[Show abstract][Hide abstract] ABSTRACT: Cerebral ischemia-reperfusion injury may simultaneously result in functional variation of multiple genes/pathways. However, most prior time-sequence studies on its pathomechanism only focused on a single gene or pathway. Our study aimed to systematically analyze the time-dependent variation in the expression of multiple pathways and networks within 24 h after cerebral ischemia-reperfusion injury.
By uploading 374 ischemia-related genes into the MetaCore software, the variation in the expression of multiple pathways and networks in 3 h, 12 h, and 24 h after cerebral ischemia-reperfusion injury had been analyzed. The conserved TNFR1-signaling pathway, among the top 10 pathways, was consistently enriched in 3 h, 12 h, and 24 h groups. Three overlapping pathways were found between 3 h and 12 h groups; 2 between 12 h and 24 h groups; and 1 between 3 h and 24 h groups. Five, 4, and 6 non-overlapping pathways were observed in 3 h, 12 h, and 24 h groups, respectively. Apart from pathways reported by earlier studies, we identified a novel pathway related to the time-dependent development of cerebral ischemia pathogenesis. The process of apoptosis stimulation by external signals, among the top 10 processes, was consistently enriched in 3 h, 12 h, and 24 h groups; 2, 1, and 2 processes overlapped between 3 h and 12 h groups, 12 h and 24 h groups, and 3 h and 24 h groups, respectively. Four, 5, and 5 non-overlapping processes were found in 3 h, 12 h and 24 h groups, respectively. The presence of apoptotic processes was observed in all the 3 groups; while anti-apoptotic processes only existed in 3 h and 12 h groups. Additionally, according to node degree, network comparison identified 1, 8,and 5 important genes or proteins (e.g. Pyk2, PKC, E2F1, and VEGF-A) in 3 h, 12 h, and 24 h groups, respectively. The Jaccard similarity index revealed a higher level of similarity between 12 h and 24 h groups than that between 3 h and 12 h groups.
Time-dependent treatment can be utilized to reduce apoptosis, which may activate anti-apoptotic pathways within 12 h after cerebral ischemia-reperfusion injury. Pathway and network analyses may help identify novel pathways and genes implicated in disease pathogenesis.
BMC Systems Biology 12/2015; 9(1):152. DOI:10.1186/s12918-015-0152-4 · 2.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Validation of pluripotent modules in diverse networks holds enormous potential for systems biology and network pharmacology. An arising challenge is how to assess the accuracy of discovering all potential modules from multi-omic networks and validating their architectural characteristics based on innovative computational methods beyond function enrichment and biological validation. To display the framework progress in this domain, we systematically divided the existing Computational Validation Approaches based on Modular Architecture (CVAMA) into topology-based approaches (TBA) and statistics-based approaches (SBA). We compared the available module validation methods based on 11 gene expression datasets, and partially consistent results in the form of homogeneous models were obtained with each individual approach, whereas discrepant contradictory results were found between TBA and SBA. The TBA of the Zsummary value had a higher Validation Success Ratio (VSR) (51%) and a higher Fluctuation Ratio (FR) (80.92%), whereas the SBA of the approximately unbiased (AU) p-value had a lower VSR (12.3%) and a lower FR (45.84%). The Gray area simulated study revealed a consistent result for these two models and indicated a lower Variation Ratio (VR) (8.10%) of TBA at 6 simulated levels. Despite facing many novel challenges and evidence limitations, CVAMA may offer novel insights into modular networks.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Reverse transcriptase polymerase chain reaction assay (RT-PCR) has been proved to have high sensitivity and specificity to detect anaplastic lymphoma kinase (ALK) rearrangements. The aim of this study was to investigate the response to crizotinib in patients of advanced non-small-cell lung cancer (NSCLC) with ALK rearrangements detected by RT-PCR.
Only patients with advanced NSCLC who had their ALK rearrangement status detected by RT-PCR were included in this analysis. The utility of RT-PCR and fluorescence in situ hybridization assay (FISH) were compared in patients who were treated with crizotinib based on their positive ALK rearrangements.
1010 patients were included in this study. Among them, 104 patients were ALK RT-PCR positive and 53 of them received crizotinib treatment. Among 255 tumors simultaneously analyzed by FISH and RT-PCR, the latter successfully detected all the 25 tumors with arrangements, including two cases that were missed by FISH. The overall response rate (ORR) and median progression free survival (mPFS) of the 53 patients with ALK rearrangements who received crizotinib treatment were 60.4% (95%CI, 47.2-73.6) and 8.4 months (95% CI 6.75-10.05) respectively, which were similar to the 21 patients detected by FISH with ORR of 57.1% (95% CI 33.3-76.2) (p=0.799) and mPFS of 7.4 months (95% CI 4.43-10.38) (p=0.833) after crizotinib treatment. Interestingly, there were 2 patients responded to crizotinib had their ALK rearrangement detected by RT-PCR but not FISH.
RT-PCR should be considered as an alternative/supplemental approach to detect ALK fusion oncogene in NSCLC patients who might benefit from crizotinib treatment.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2015; 10(11). DOI:10.1097/JTO.0000000000000668 · 5.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our previous studies have showed that ursodeoxycholic acid (UA) and jasminoidin (JA) effectively reduce cerebral infarct volume in mice. In this study we explored the pure synergistic mechanism of these compounds in treatment of mouse cerebral ischemia, which was defined as synergistic actions specific for phenotype variations after excluding interference from ineffective compounds.
Mice with focal cerebral ischemia were treated with UA, JA or a combination JA and UA (JU). Concha margaritifera (CM) was taken as ineffective compound. Cerebral infarct volume of the mice was determined, and the hippocampi were taken for microarray analysis. Particular signaling pathways and biological functions were enriched based on differentially expressed genes, and corresponding networks were constructed through Ingenuity Pathway Analysis.
In phenotype analysis, UA, JA and JU significantly reduced the ischemic infarct volume with JU being superior to UA or JA alone, while CM was ineffective. As a result, 4 pathways enriched in CM were excluded. Core pathways in the phenotype-positive groups (UA or JA) were involved in neuronal homeostasis and neuropathology. JU-contributing pathways included all UA-contributing and the majority (71.7%) of JA-contributing pathways, and 10 new core pathways whose effects included inflammatory immunity, apoptosis and nervous system development. The functions of JU group included all functions of JA group, the majority (93.1%) of UA-contributing functions, and 3 new core functions, which focused on physiological system development and function.
The pure synergism between UA and JA underlies 10 new core pathways and 3 new core functions, which are involved in inflammation, immune responses, apoptosis and nervous system development.
[Show abstract][Hide abstract] ABSTRACT: To determine how the relative amino acid contents and metabolic pathways regulate the pharmacological phenotypes in rats with cerebral ischemia after treatment with varying doses of DanHong injection (DHI).
Adult male rats underwent middle cerebral artery occlusion (MCAO), and were injected with DHI (DH-1: 1 mL/kg; DH-2: 2.5 mL/kg; DH-3: 5 mL/kg, and DH-4: 10 mL/kg, iv) daily for 3 d. The neurological deficit score, body weights and infarct volume were assessed. Serum levels of 20 free amino acids were determined using HPLC, and the values were transformed through the quantitative analysis of the amino acids in the serum metabolic spectrum. Multivariate statistical analysis methods (PCA and PLS-DA) and web-based metabolomics tools (MetPa and MetaboAnalyst) were used to analyze the biological data sets for the amino acids.
Administration of DHI dose-dependently decreased cerebral infarct volume, and ameliorated neurological deficits. A total of 5, 6, 7 and 7 non-overlapping metabolites were identified in the DH-1, DH-2, DH-3, and DH-4 groups, respectively. Eight metabolites were shared between the DHI groups and the vehicle group. In addition, the serum levels of glutamic acid, aspartic acid and serine increased with increasing DHI dose. A total of 3, 2, 2 and 5 non-overlapping metabolic pathways were identified in the DH-1, DH-2, DH-3 and DH-4 groups, respectively, and glycine, serine, threonine and histidine metabolism were identified as overlapping pathways among the 4 dose groups.
Overlapping and non-overlapping amino acid metabolites and metabolic pathways are associated with the dose-dependent neuroprotective effect of DHI.
[Show abstract][Hide abstract] ABSTRACT: Nb doped TiO2 microspheres modified with WO3 (Nb-TiO2/WO3) was prepared by ultrasonic spray pyrolysis method combined with impregnation method. The microspheres were characterized with SEM, TEM, XRD, BET, photoluminescence and UV-vis absorption spectra. The Nb-doping was observed to extend the spectral absorption of TiO2 into visible spectrum, and the absorption onset was red-shifted for about 88 nm compared to pristine TiO2 microspheres. Nb-TiO2/WO3 microspheres do not display a red-shifted absorption edge compared with Nb doped TiO2 microspheres. Under solar irradiation, Nb-TiO2/WO3 microspheres showed higher photocatalytic activity for methylene blue degradation compared with that of pure TiO2 microspheres and Nb doped TiO2 microspheres, which could be ascribed to the extended light absorption range and the suppression of electron-hole pair recombination.
Materials Research Bulletin 03/2015; 63:105-111. DOI:10.1016/j.materresbull.2014.11.050 · 2.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the effectiveness of double arthrodesis to correct flatfoot deformity with pes valgus.
Between May 2009 and May 2012, 12 patients with flatfoot deformity and pes valgus were treated using subtalar and talonavicular joints arthrodesis through a single medial incision approach. There were 5 males and 7 females with an average age of 53.3 years (range, 21-78 years), including 5 left feet and 7 right feet. Of them, 11 cases had posterior tibial tendon dysfunctions; 6 cases were at Johnson-Strom stage III, 5 cases at stage II(c); and 1 case had tarsal coalition. Preoperative American Orthopaedic Foot and Ankle Society (AOFAS) score and visual analogue scale (VAS) score were 48.75 ± 3.46 and 6.08 ± 1.14, respectively.
The mean operation time was 85.6 minutes (range, 65-125 minutes). Eleven patients were followed up for 19.4 months on average (range, 13-30 months). All of the cases obtained primary healing of incision, with no complication of infection and nerve or blood vessel injury. X-ray film showed that the mean time of bone union was 9.8 weeks (range, 7-18 weeks): no bone nonunion occurred. No loosening or breakage of internal fixation was observed. Pain occurred at the calcaneal-cuboid joint (1 case) and at fixation site (1 case), and was relieved after symptomatic treatment. The mean AOFAS score and VAS score were significantly increased to 81.36 ± 2.98 and 0.72 ± 0.11 respectively, showing significant differences when compared with preoperative scores (t = 19.946, P = 0.000; t = 16.288, P = 0.000).
Subtalar and talonavicular joints arthrodesis by a single medial incision approach is a useful alternative to triple arthrodesis for the correction of flatfoot deformity with pes valgus.
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery 11/2014; 28(11):1321-4.
[Show abstract][Hide abstract] ABSTRACT: According to the principle of evidence-based medicine (EBM), Chinese medical literatures based descriptive statistical analysis of common Chinese medical syndrome types were performed. By data extraction, standardization, and frequency calculation of disease names and syndrome types from 286 literatures in line with the inclusion criteria, the frequencies of diseases and syndromes were obtained to analyze common syndrome types in clinical practice, to analyze the distribution features of disease related syndromes and syndrome related diseases, to analyze the distribution of basic Chinese medical syndrome types in clinical common diseases as a whole, thus providing reference for clinical and basic researches.
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban 08/2014; 34(8):1013-6.
[Show abstract][Hide abstract] ABSTRACT: Di-(2-ethylhexyl) phthalate, as the most commonly used plasticizer, is considered to be related to the asthma prevalence. There are studies affirming that the DEHP has an adjuvant effect in the pathogenesis of allergy asthma. Oxidative stress is one possible pathway for DEHP-adjuvant effect. Thus, this study explored whether DEHP could induce adjuvant effect in mouse asthma model via oxidative stress pathway. Male BALB/c mice were randomly divided into six groups: (1) saline group, (2) DEHP group, (3) ovalbumin (OVA) group, (4) DEHP+OVA group, (5) OVA +vitamin E (Vit E) group, (6) DEHP+OVA+Vit E group. The exposure dose of DEHP was 30 mg/kg body weight (bw)/day. After 18 days of the exposure protocol. Reactive oxygen species (ROS), glutathione (GSH) and malonaldehyde (MDA) levels and biomarkers related to asthma model were measured. Collectively, these data indicated higher ROS and MDA levels and lower GSH contents in DEHP+OVA group than that in OVA group, while Vit E, an antioxidant, could restore ROS, MDA and GSH levels to control levels and attenuate the DEHP and/or OVA effects. Our observations suggested that there was a relationship between oxidative stress and the adjuvant effect induced by DEHP in this mouse asthma model.
Food and Chemical Toxicology 06/2014; 71. DOI:10.1016/j.fct.2014.06.012 · 2.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Posterior pilon fractures are rare injuries and have not yet gained well recognition. The purpose of this study was to present the treatment outcome for patients with posterior pilon fractures treated with buttress plate.
In this retrospective study we identified patients with posterior pilon fractures of the distal tibia who had undergone open reduction and internal fixation at our institute. Between January 2007 and December 2009, 10 patients (mean age, 46.5 years) who had undergone buttress plating via either a posterolateral approach or a dual posterolateral-posteromedial approach, were selected. All 10 patients were available for follow-up. The clinical outcome was evaluated with the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the visual analogue scale (VAS). The radiological evaluation was performed using the osteoarthritis-score (OA-score).
Satisfactory reduction and stable fixation were accomplished in all patients. At a mean follow-up of 36.2 months, all patients had good radiological results and showed satisfactory clinical recovery. The mean AOFAS sore was 87.8, the mean OA-score was 0.6, and the mean VAS scores during rest, active motion, and weight-bearing walking were 0.6, 0.8, and 1.4, respectively.
Buttress plating for posterior pilon fractures gave satisfactory clinical outcomes. It also ensured rigid fixation which in turn enabled earlier postoperative mobilization. Level of Evidence IV, Retrospective Study.
[Show abstract][Hide abstract] ABSTRACT: TiO2-graphene porous microspheres were prepared by ultrasonic spray pyrolysis (USP) of aqueous suspension of graphene oxide containing TiO2 nanoparticles (Degussa P25). The composite microspheres were characterized with SEM, XPS, photoluminescence, Raman and UV-Vis absorption spectra. TiO2-graphene porous microspheres displayed higher photocatalytic activity for the degradation of methylene blue solution than pristine TiO2 microspheres under the irradiation of Xe lamp, and the highest activity was obtained at a weight percentage of graphene around 1%. The effect of graphene on photocatalytic activity of porous microsphere was discussed in terms of the enhanced charge separation by TiO2-graphene heterojunction, increased absorption of the visible light, as well as the possible hindrance of mass transportation in microspheres.
Journal of Alloys and Compounds 01/2014; 584:180-184. DOI:10.1016/j.jallcom.2013.08.203 · 3.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To explore the anatomy of the plantar aponeurosis (PA) and its biomechanical effects on the first metatarsophalangeal (MTP) joint and foot arch.
Anatomic parameters (length, width and thickness of each central PA bundle and the main body of the central part) were measured in 8 cadaveric specimens. The ratios of the length and width of each bundle to the length and width of the central part were used to describe these bundles. Six cadaveric specimens were used to measure the range of motion of the first MTP joint before and after releasing the first bundle of the PA. Another 6 specimens were used to evaluate simulated static weight-bearing. Changes in foot arch height and plantar pressure were measured before and after dividing the first bundle.
The average width and thickness of the origin of the central part at the calcaneal tubercle were 15.45 mm and 2.79 mm respectively. The ratio of the length of each bundle to the length of the central part was (from medial to lateral) 0.29, 0.30, 0.28, 0.25, and 0.27, respectively. Similarly, the ratio of the widths was 0.26, 0.25, 0.23, 0.19 and 0.17. The thickness of each bundle at the bifurcation of the PA into bundles was (from medial to lateral) 1.26 mm, 1.04 mm, 0.91 mm, 0.84 mm and 0.72 mm. The average dorsiflexion of the first MTP joint increased 10.16° after the first bundle was divided. Marked acute changes in the foot arch height and the plantar pressure were not observed after division.
The first PA bundle was not the longest, widest, or the thickest bundle. Releasing the first bundle increased the range of motion of the first MTP joint, but did not acutely change foot arch height or plantar pressure during static load testing.
PLoS ONE 01/2014; 9(1):e84347. DOI:10.1371/journal.pone.0084347 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Waveband-dependent photochemical reduction properties of graphene oxide (GO) were investigated. The ratio of oxygenated carbon to graphitic carbon of the GO film was reduced to 39% and 28% by 400-800 nm and 350-800 nm irradiation, respectively from the initial value of 47%, while this ratio changed negligibly by 520-800 nm irradiation. This waveband-dependent photoreduction is closely related to the wide size distribution of sp2 carbon clusters with different band gaps within the GO sheet, which play the role of the photochemical reacting centers. In addition, the photochemical activity of GO was also demonstrated by photoreduction of Ag+ in water. Our research suggests the possibilities of tuning the microstructure of GO by careful selection of irradiation conditions and of preparing noble metal nanoparticles with a neat surface on GO sheets.