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1.  Impaired Varus-Valgus Proprioception and Neuromuscular Stabilization in Medial Knee Osteoarthritis 
Journal of biomechanics  2013;47(2):360-366.
Impaired proprioception and poor muscular stabilization in the frontal plane may lead to knee instability during functional activities, a common complaint in persons with knee osteoarthritis (KOA). Understanding these frontal plane neuromechanical properties in KOA will help elucidate the factors contributing to knee instability and aid in the development of targeted intervention strategies. The study objectives were to compare knee varus-valgus proprioception, isometric muscle strength, and active muscular contribution to stability between persons with medial KOA and healthy controls. We evaluated knee frontal plane neuromechanical parameters in 14 participants with medial KOA and 14 age- and gender-matched controls, using a joint driving device (JDD) with a customized motor and a 6-axis force sensor. Analysis of covariance with BMI as a covariate was used to test the differences in varus-valgus neuromechanical parameters between these two groups. The KOA group had impaired varus proprioception acuity (1.08 ± 0.59° vs. 0.69 ± 0.49°, p < 0.05), decreased normalized varus muscle strength (1.31 ± 0.75% vs. 1.79 ± 0.84% body weight, p < 0.05), a trend toward decreased valgus strength (1.29 ± 0.67% vs. 1.88 ± 0.99%, p = 0.054), and impaired ability to actively stabilize the knee in the frontal plane during external perturbation (4.67 ± 2.86 vs. 8.26 ± 5.95 Nm/degree, p < 0.05). The knee frontal plane sensorimotor control system is compromised in persons with medial KOA. Our findings suggest varus-valgus control deficits in both the afferent input (proprioceptive acuity) and muscular effectors (muscle strength and capacity to stabilize the joint).
PMCID: PMC3929588  PMID: 24321442
Knee osteoarthritis; Proprioception; Instability; Varus-valgus motion
2.  Moderate Hypothermia Inhibits Brain Inflammation and Attenuates Stroke-induced Immunodepression in Rats 
CNS neuroscience & therapeutics  2013;20(1):10.1111/cns.12160.
Stroke causes both brain inflammation and immunodepression. Mild to moderate hypothermia is known to attenuate brain inflammation but its role in stroke-induced immunodepression (SIID) of the peripheral immune system remains unknown. This study investigated the effects in rats of moderate intra-ischemic hypothermia on SIID and brain inflammation.
Stroke was induced in rats by permanent distal MCA occlusion combined with transient bilateral CCA occlusion while body temperature was reduced to 30°C. Real-time PCR, flow cytometry, in vitro T cell proliferation assays and confocal microscopy were used to study SIID and brain inflammation.
Brief Intra-Ischemic hypothermia helped maintain certain leukocytes in the peripheral blood and spleen, and enhanced T cell proliferation in vitro and delayed-type hypersensitivity in vivo, suggesting that hypothermia reduces SIID. In contrast, in the brain, brief intra-Ischemic hypothermia inhibited mRNA expression of anti-inflammatory cytokine IL-10 and pro-inflammatory cytokines INF-γ, TNF-α, IL-2, IL-1β and MIP-2. Brief intra-Ischemic hypothermia also attenuated the infiltration of lymphocytes, neutrophils (MPO+ cells) and macrophages (CD68+ cells) into the ischemic brain, suggesting that hypothermia inhibited brain inflammation.
Brief intra-ischemic hypothermia attenuated SIID and protected against acute brain inflammation.
PMCID: PMC3867545  PMID: 23981596
focal cerebral ischemia; hypothermia; inflammation; immunodepression; leukocytes
3.  Akt isoforms differentially protect against stroke-induced neuronal injury by regulating mTOR activities 
Protein kinases Akt1 and Akt3 are considered to be more crucial to brain function than Akt2. We investigated the roles of Akt1 and Akt3 in stroke-induced brain injury and examined their interactions with the Akt/mTOR pathways. Focal ischemia was induced in rats. Lentiviral vectors expressing constitutively active Akt1 and Akt3 (cAkt1 and cAkt3) were injected into the ischemic cortex. Infarct sizes and gene and protein expressions in the Akt/mTOR pathways were evaluated. The results show that Akt1 and Akt3 proteins were degraded as early as 1 hour after stroke, whereas Akt2 proteins remained unchanged until 24 hours after stroke. Lentiviral-mediated overexpression of cAkt1 or cAkt3 reduced neuronal death after in vitro and in vivo ischemia. Interestingly, cAkt3 overexpression resulted in stronger protection than cAkt1 overexpression. Western blot analyses further showed that cAkt3 promoted significantly higher levels of phosphorylated Akt and phosphorylated mTOR than cAkt1. The mTOR inhibitor rapamycin blocked the protective effects of both cAkt1 and cAkt3. In conclusion, Akt isoforms are differentially regulated after stroke and Akt3 offers stronger protection than cAkt1 by maintaining Akt levels and promoting mTOR activity.
PMCID: PMC3851893  PMID: 23942361
Akt1; Akt3; cerebral ischemia; mTOR; stroke
4.  Ischemic postconditioning facilitates brain recovery after stroke by promoting Akt/mTOR activity in nude rats 
Journal of neurochemistry  2013;127(5):723-732.
While preconditioning is induced before stroke onset, ischemic postconditioning (IPostC) is performed after reperfusion, which typically refers to a series of mechanical interruption of blood reperfusion after stroke. IPostC is known to reduce infarction in wild type animals. We investigated if IPostC protects against brain injury induced by focal ischemia in T-cell-deficient nude rats and to examine its effects on Akt and the mammalian target of rapamycin (mTOR) pathway. Although IPostC reduced infarct size at 2 days post-stroke in wild type rats, it did not attenuate infarction in nude rats. Despite the unaltered infarct size in nude rats, IPostC increased levels of phosphorylated Akt (p-Akt) and Akt isoforms (Akt1, Akt2, Akt3), and p-mTOR, p-S6K and p-4EBP1 in the mTOR pathway, as well as GAP-43, both in the peri-infarct area and core, 24 hours after stroke. IPostC improved neurological function in nude rats 1–30 days after stroke and reduced the extent of brain damage 30 days after stroke. The mTOR inhibitor rapamycin abolished the long-term protective effects of IPostC. We determined that IPostC did not inhibit acute infarction in nude rats but did provide long-term protection by enhancing Akt and mTOR activity during the acute post-stroke phase.
PMCID: PMC3875603  PMID: 23777415
Stroke; Ischemic postconditioning; T cells; Akt; mTOR
5.  A C-Terminal Proline-Rich Sequence Simultaneously Broadens the Optimal Temperature and pH Ranges and Improves the Catalytic Efficiency of Glycosyl Hydrolase Family 10 Ruminal Xylanases 
Applied and Environmental Microbiology  2014;80(11):3426-3432.
Efficient degradation of plant polysaccharides in rumen requires xylanolytic enzymes with a high catalytic capacity. In this study, a full-length xylanase gene (xynA) was retrieved from the sheep rumen. The deduced XynA sequence contains a putative signal peptide, a catalytic motif of glycoside hydrolase family 10 (GH10), and an extra C-terminal proline-rich sequence without a homolog. To determine its function, both mature XynA and its C terminus-truncated mutant, XynA-Tr, were expressed in Escherichia coli. The C-terminal oligopeptide had significant effects on the function and structure of XynA. Compared with XynA-Tr, XynA exhibited improved specific activity (12-fold) and catalytic efficiency (14-fold), a higher temperature optimum (50°C versus 45°C), and broader ranges of temperature and pH optima (pH 5.0 to 7.5 and 40 to 60°C versus pH 5.5 to 6.5 and 40 to 50°C). Moreover, XynA released more xylose than XynA-Tr when using beech wood xylan and wheat arabinoxylan as the substrate. The underlying mechanisms responsible for these changes were analyzed by substrate binding assay, circular dichroism (CD) spectroscopy, isothermal titration calorimetry (ITC), and xylooligosaccharide hydrolysis. XynA had no ability to bind to any of the tested soluble and insoluble polysaccharides. However, it contained more α helices and had a greater affinity and catalytic efficiency toward xylooligosaccharides, which benefited complete substrate degradation. Similar results were obtained when the C-terminal sequence was fused to another GH10 xylanase from sheep rumen. This study reveals an engineering strategy to improve the catalytic performance of enzymes.
PMCID: PMC4018843  PMID: 24657866
6.  Study on the Traffic Air Pollution inside and outside a Road Tunnel in Shanghai, China 
PLoS ONE  2014;9(11):e112195.
To investigate the vehicle induced air pollution situations both inside and outside the tunnel, the field measurement of the pollutants concentrations and its diurnal variations was performed inside and outside the Xiangyin tunnel in Shanghai from 13:00 on April 24th to 13:00 on April 25th, 2013. The highest hourly average concentrations of pollutants were quantified that CO, NO, NO2 and NOX inside the tunnel were 13.223 mg/m3, 1.829 mg/m3, 0.291 mg/m3 and 3.029 mg/m3, respectively, while the lowest ones were 3.086 mg/m3, 0.344 mg/m3, 0.080 mg/m3 and 0.619 mg/m3. Moreover, the concentrations of pollutants were higher during the daytime, and lower at night, which is relevant to the traffic conditions inside the tunnel. Pollutants concentrations inside the tunnel were much higher than those outside the tunnel. Then in a case of slow wind, the effect of wind is much smaller than the impact of pollution sources. Additionally, the PM2.5 concentrations climbed to the peak sharply (468.45 µg/m3) during the morning rush hours. The concentrations of organic carbon (OC) and elemental carbon (EC) in PM2.5 inside the tunnel were 37.09–99.06 µg/m3 and 22.69–137.99 µg/m3, respectively. Besides, the OC/EC ratio ranged from 0.72 to 2.19 with an average value of 1.34. Compared with the results of other tunnel experiments in Guangzhou and Shenzhen, China, it could be inferred that the proportion of HDVs through the Xiangyin tunnel is relatively lower.
PMCID: PMC4227705  PMID: 25386920
7.  Ranking candidate genes of esophageal squamous cell carcinomas based on differentially expressed genes and the topological properties of the co-expression network 
The aim of this study was to identify the candidate genes of esophageal squamous cell carcinoma (ESCC).
Gene expression profiling of 17 ESCC samples and 17 adjacent normal samples, GSE20347, was downloaded from Gene Expression Omnibus database. The raw data were preprocessed, and the differentially expressed genes (DEGs) between ESCC and normal samples were identified by using SAM software (false discovery rate <0.001). Then, the co-expression network of DEGs was constructed based on Pearson’s correlation test (r-value ≥0.8). Furthermore, the topological properties of the co-expression network were analyzed through NetworkAnalyzer (default settings) of Cytoscape. The expression fold changes of DEGs and topological properties were utilized to identify the candidate genes of ESCC (Crin score >4), which were further analyzed based on DAVID functional enrichment analysis (P-value <0.05).
A total of 1,063 DEGs were identified, including 490 up-regulated and 573 down-regulated DEGs. Then, the co-expression network of DEGs was constructed, containing 999 nodes and 46,323 edges. Based on the expression fold changes of DEGs and the topological properties of the co-expression network, DEGs were ranked, and the top 24 genes were candidate genes of ESCC, such as CRISP3, EREG, CXCR2, and CRNN. Furthermore, the 24 genes were significantly enriched in bio-functions regarding cell differentiation, glucan biosynthetic process and immune response.
The present study suggested that CRISP3, EREG, CXCR2, and CRNN might be causative genes of ESCC, and play vital roles in the development of ESCC. However, further experimental studies are needed to confirm our results.
Electronic supplementary material
The online version of this article (doi:10.1186/s40001-014-0052-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4223754  PMID: 25358439
Esophageal squamous cell carcinomas; Differentially expressed genes; Topological properties; Co-expression network; Candidate genes
8.  Comb-push Ultrasound Shear Elastography (CUSE) with Various Ultrasound Push Beams 
IEEE transactions on medical imaging  2013;32(8):1435-1447.
Comb-push Ultrasound Shear Elastography (CUSE) has recently been shown to be a fast and accurate two-dimensional (2D) elasticity imaging technique that can provide a full field-of- view (FOV) shear wave speed map with only one rapid data acquisition. The initial version of CUSE was termed U-CUSE because unfocused ultrasound push beams were used. In this paper, we present two new versions of CUSE – Focused CUSE (F-CUSE) and Marching CUSE (M-CUSE), which use focused ultrasound push beams to improve acoustic radiation force penetration and produce stronger shear waves in deep tissues (e.g. kidney and liver). F-CUSE divides transducer elements into several subgroups which transmit multiple focused ultrasound beams simultaneously. M-CUSE uses more elements for each focused push beam and laterally marches the push beams. Both F-CUSE and M-CUSE can generate comb-shaped shear wave fields that have shear wave motion at each imaging pixel location so that a full FOV 2D shear wave speed map can be reconstructed with only one data acquisition. Homogeneous phantom experiments showed that U-CUSE, F-CUSE and M-CUSE can all produce smooth shear wave speed maps with accurate shear wave speed estimates. An inclusion phantom experiment showed that all CUSE methods could provide good contrast between the inclusion and background with sharp boundaries while F-CUSE and M-CUSE require shorter push durations to achieve shear wave speed maps with comparable SNR to U-CUSE. A more challenging inclusion phantom experiment with a very stiff and deep inclusion shows that better shear wave penetration could be gained by using F-CUSE and M-CUSE. Finally, a shallow inclusion experiment showed that good preservations of inclusion shapes could be achieved by both U-CUSE and F-CUSE in the near field. Safety measurements showed that all safety parameters are below FDA regulatory limits for all CUSE methods. These promising results suggest that, using various push beams, CUSE is capable of reconstructing a 2D full FOV shear elasticity map using only one push-detection data acquisition in a wide range of depths for soft tissue elasticity imaging.
PMCID: PMC3760382  PMID: 23591479
CUSE; comb-push; ultrasound elastography; shear wave; acoustic radiation force; unfocused ultrasound beam; focused ultrasound beam
9.  Ischemic postconditioning protects against focal cerebral ischemia by inhibiting brain inflammation while attenuating peripheral lymphopenia in mice 
Neuroscience  2013;243:149-157.
Ischemic postconditioning (IPostC) has been shown to attenuate brain injury in rat stroke models, but a mouse model has not been reported. This study establishes an IPostC model in mice and investigates how IPostC affects infiltration of leukocytes in the ischemic brain and lymphopenia associated with stroke-induced immunodepression.
Material and Methods
A total of 125 mice were used. IPostC was performed by a repeated series of brief occlusions of the middle cerebral artery (MCA) after reperfusion, in a focal ischemia model in mice. Infarct sizes, neurological scores, inflammatory brain cells and immune cell populations in lymph nodes, spleen and bone marrow were analyzed with FACS.
IPostC performed immediately, 2 min and 3 hr after reperfusion significantly reduced infarct sizes and attenuated neurological scores as measured up to 3 days post-stroke. In the group with strongest protection, infarct sizes were reduced from 49.6 ± 2.8% (n=16) to 27.9 ± 2.9% (n=10, P<.001). The spared infarct areas were seen in the ischemic penumbra or ischemic margins, i.e., the border zones between the cortical territories of the anterior cerebral artery (ACA) and those of the MCA, as well as in the ventromedial and dorsolateral striatum. FACS analyses showed that IPostC significantly blocked increases in the numbers of microglia (CD45intCD11b+), macrophages (CD45hiCD68+), CD4 T cells (CD45+CD4+) and CD8 T cells (CD45+CD8+) as well as B lymphocytes (CD45+CD19+) in the ischemic brain (n=5/group). Reduced-immune cell numbers in the peripheral blood and spleen were increased by IPostC while immune cell populations in the bone marrow were not altered by IPostC.
IPostC reduced brain infarction and mitigated neurological deficits in mice, likely by blocking infiltration of both innate and adaptive immune cells in the ischemic brain. In addition, IPostC robustly attenuated peripheral lymphopenia and thus improved systemic immunodepression.
PMCID: PMC3735351  PMID: 23590905
cerebral ischemia; postconditioning; infarction size; mouse model
10.  Primary intrathoracic liposarcoma: a clinicopathologic study and prognostic analysis of 23 cases 
Primary intrathoracic liposarcoma is an extremely rare malignancy as well as a rare histologic subtype of intrathoracic sarcoma. Relatively few reports appear in the world literatures. We explored the clinicopathologic features and prognostic factors of this tumor in this study.
We retrospectively analyzed the clinicopathological data of 23 patients with primary intrathoracic liposarcoma who were treated in Shanghai chest Hospital affiliated to Jiao Tong University, from January 2003 to March 2013. These patients were classified into three groups according to the distinct tumor locations, including mediastinum, pleura and lung liposarcoma. Also, these patients could be divided into four types, including well-differentiated, myxoid, dedifferentiated and pleomorphic liposarcoma. The influences of age, sex, tumor size, tumor location, tumor histologic type and therapy on the prognosis of the patients were analyzed.
There were no significant difference for survival among distinct liposarcoma locations. However, significant difference for survival among distinct liposarcoma types were observed. Poor disease-free survival (DFS) was observed in the myxoid, pleomorphic and dedifferentiated types as compared to well-differentiated type (P = 0.038). Inferior overall-survival (OS) was observed in dedifferentiated, pleomorphic and myxoid types relative to well-differentiated type (P = 0.027). The radical surgery was a favorable prognostic factor for OS, as demonstrated by the better OS of the radical surgery group as compared to that of the non-radical surgery group ( P = 0.029). Notably, there were no significant differences for DFS and OS in other clinical parameters including tumor size, gender and age. In addition, radiotherapy and/or chemotherapy could not improve the prognosis of the patients receiving non-radical surgery or suffering from relapse.
The histological type and the radical surgery are the factors that influence the behavior and prognosis of liposarcoma. In general, radiotherapy and chemotherapy are believed to be ineffective therapeutic modalities for survival. So it is essential to completely resect the primary intrathoracic liposarcoma as radical cure of the disease.
PMCID: PMC4088306  PMID: 24993036
Intrathoracic liposarcoma; Histological type; Radical surgery; Overall survival; Disease-free survival
11.  Altered functional brain networks in Prader–Willi syndrome 
NMR in biomedicine  2013;26(6):10.1002/nbm.2900.
Prader–Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous functional neuroimaging studies used visual stimuli to examine abnormal activities in the eating-related neural circuitry of patients with PWS. It was found that patients with PWS exhibited both excessive hunger and hyperphagia consistently, even in situations without any food stimulation. In the present study, we employed resting-state functional MRI techniques to investigate abnormal brain networks related to eating disorders in children with PWS. First, we applied amplitude of low-frequency fluctuation analysis to define the regions of interest that showed significant alterations in resting-state brain activity levels in patients compared with their sibling control group. We then applied a functional connectivity (FC) analysis to these regions of interest in order to characterize interactions among the brain regions. Our results demonstrated that patients with PWS showed decreased FC strength in the medial prefrontal cortex (MPFC)/inferior parietal lobe (IPL), MPFC/precuneus, IPL/precuneus and IPL/hippocampus in the default mode network; decreased FC strength in the pre-/postcentral gyri and dorsolateral prefrontal cortex (DLPFC)/orbitofrontal cortex (OFC) in the motor sensory network and prefrontal cortex network, respectively; and increased FC strength in the anterior cingulate cortex/insula, ventrolateral prefrontal cortex (VLPFC)/OFC and DLPFC/VLPFC in the core network and prefrontal cortex network, respectively. These findings indicate that there are FC alterations among the brain regions implicated in eating as well as rewarding, even during the resting state, which may provide further evidence supporting the use of PWS as a model to study obesity and to provide information on potential neural targets for the medical treatment of overeating.
PMCID: PMC3776442  PMID: 23335390
Prader; Willi syndrome; eating disorder; obesity; amplitude of low-frequency fluctuation; resting-state networks; functional MRI
12.  Factors that predict lymph node status in clinical stage T1aN0M0 lung adenocarcinomas 
To identify patients in whom systematic lymph node dissection would be suitable, preoperative diagnosis of the biological invasiveness of lung adenocarcinomas through the classification of these T1aN0M0 lung adenocarcinomas into several subgroups may be warranted. In this retrospective study, we sought to determine predictive factors of lymph node status in clinical stage T1aN0M0 lung adenocarcinomas.
We retrospectively reviewed the records of 273 consecutive patients undergone surgical resection of clinical stage T1aN0M0 lung adenocarcinomas at Shanghai Chest Hospital, from January 2011 to December 2012. Preoperative computed tomography findings of all 273 patients were reviewed and their tumors categorized as pure GGO, GGO with minimal solid components (<5 mm), part-solid (solid parts >5 mm), or purely solid. Relevant clinicopathologic features were investigated to identify predictors of hilar or mediastinal lymph node metastasis using univariate or multiple variable analysis.
Among the 273 eligible clinical stage T1aN0M0 lung adenocarcinomas examined on thin-section CT, 103 (37.7%) were pure GGO, 118 (43.2%) GGO with minimal solid components, 13 (4.8%) part-solid (solid parts >5 mm, five GGO predominant and eight solid predominant), and 39 (14.3%) pure solid. There were 18 (6.6%) patients with lymph node metastasis. Incidence of N1 and N2 nodal involvement was 11 (6.6%) and seven (2.6%) patients, respectively. All patients with pure GGO and GGO with minimal solid components (<5 mm) tumors were pathologically staged N0. Multivariate analyses showed that the following factors significantly predicted lymph node metastasis for T1a lung adenocarcinomas: symptoms at presentation, GGO status, and abnormal carcinoembryonic antigen (CEA) titer. Multivariate analyses also showed that the following factors significantly predicted lymph node metastasis for pure solid tumors: air bronchogram sign, tumor size, symptoms at presentation, and abnormal CEA titer.
The patients of clinical stage T1aN0M0 lung adenocarcinomas with pure GGO and GGO with minimal solid components tumors were pathologically staged N0 and systematic lymph node dissection should be avoided. But systematic lymph node dissection should be performed for pure solid tumors or part-solid, especially in patients with CEA greater than 5 ng/mL or symptoms at presentation, because of the high possibility of lymph node involvement.
PMCID: PMC3945801  PMID: 24559138
Lymph node; Lung adenocarcinomas; Stage small non-small cell lung cancer
13.  The protective effects of T cell deficiency against brain injury are ischemic model-dependent in rats 
Neurochemistry international  2012;62(3):265-270.
Previous studies have reported that T cell deficiency reduced infarct sizes after transient middle cerebral artery (MCA) suture occlusion in mice. However, how reperfusion and different models affect the detrimental effects of T cells have not been studied. We investigated the effects of T cell deficiency in nude rats using two stroke models and compared their infarct sizes with those in WT rats. In the distal MCA occlusion (MCAo) model, the distal MCA was permanently occluded and the bilateral common carotid arteries (CCAs) were transiently occluded for 60 min. In the suture MCAo model, the MCA was transiently occluded for 100 min by the insertion of a monofilament suture. Our results showed that T cell deficiency resulted in about a 50% reduction in infarct size in the suture MCAo model, whereas it had no effect in the distal MCAo model, suggesting the protective effects of T cell deficiency are dependent on the ischemic model used. We further found more total T cells, CD4 T cells and CD8 T cells in the ischemic brains of WT rats in the suture MCAo model than in the distal MCAo model. In addition, we detected more CD68-expressing macrophages in the ischemic brains of WT rats than in nude rats in the suture MCAo but not the distal MCAo model. Lymphocyte reconstitution in nude rats resulted in larger infarct sizes in the suture MCAo, but not in the distal MCAo stroke model. The results of regional CBF measurement indicated a total reperfusion in the MCAo model but only a partial reperfusion in the distal MCAo model. In conclusion, the protective effects of T cell deficiency on brain injury are dependent on the ischemic model used; likely associated with different degrees of reperfusion.
PMCID: PMC3581747  PMID: 23228347
Stroke; focal ischemia; nude rats T cells
14.  Hurdles to clear before clinical translation of ischemic postconditioning against stroke 
Translational stroke research  2013;4(1):63-70.
Ischemic postconditioning has been established for its protective effects against stroke in animal models. It is performed after post-stroke reperfusion and refers to a series of induced ischemia or a single brief one. This review article addresses major hurdles in clinical translation of ischemic postconditioning to stroke patients, including potential hazards, the lack of well-defined protective paradigms, and the paucity of deeply-understood protective mechanisms. A hormetic model, often used in toxicology to describe a dose-dependent response to a toxic agent, is suggested to study both beneficial and detrimental effects of ischemic postconditioning. Experimental strategies are discussed, including how to define the hazards of ischemic (homologous) postconditioning and the possibility of employing non-ischemic (heterologous) postconditioning to facilitate clinical translation. This review concludes that a more detailed assessment of ischemic postconditioning and studies of a broad range of heterologous postconditioning models are warranted for future clinical translation.
PMCID: PMC3601799  PMID: 23524538
ischemic postconditioning; preconditioning; stroke; hormesis; clinical translation
15.  A Part-Based Probabilistic Model for Object Detection with Occlusion 
PLoS ONE  2014;9(1):e84624.
The part-based method has been a fast rising framework for object detection. It is attracting more and more attention for its detection precision and partial robustness to the occlusion. However, little research has been focused on the problem of occlusion overlapping of the part regions, which can reduce the performance of the system. This paper proposes a part-based probabilistic model and the corresponding inference algorithm for the problem of the part occlusion. The model is based on the Bayesian theory integrally and aims to be robust to the large occlusion. In the stage of the model construction, all of the parts constitute the vertex set of a fully connected graph, and a binary variable is assigned to each part to indicate its occlusion status. In addition, we introduce a penalty term to regularize the argument space of the objective function. Thus, the part detection is formulated as an optimization problem, which is divided into two alternative procedures: the outer inference and the inner inference. A stochastic tentative method is employed in the outer inference to determine the occlusion status for each part. In the inner inference, the gradient descent algorithm is employed to find the optimal positions of the parts, in term of the current occlusion status. Experiments were carried out on the Caltech database. The results demonstrated that the proposed method achieves a strong robustness to the occlusion.
PMCID: PMC3894947  PMID: 24465420
16.  Safety and efficacy of thoracoscopic wedge resection for elderly high-risk patients with stage I peripheral non-small-cell lung cancer 
Elderly patients with severe cardiopulmonary and other system dysfunctions are unable to tolerate pulmonary lobectomy. This study aimed to evaluate the risk and efficacy of wedge resection under video-assisted thoracoscopic surgery (VATS) on elderly high-risk patients with stage I peripheral non-small-cell lung cancer (PNSCLC).
Elderly patients (≥70 years) with suspected PNSCLC were divided into high-risk group and conventional risk group. The high-risk patients confirmed in stage I by the examination of positron emission tomography computed tomography (PET-CT) and the postoperative patients in stage I PNSCLC with negative incisal margin were treated with VATS wedge resection. The conventional risk patients were treated with VATS radical resection and systematic lymphadenectomy. The clinical and pathological data were recorded. The total survival, tumor-free survival, recurrence time and style of patients were followed up.
The operative time and blood loss of the VATS wedge resection group (69.4 ± 15.5 min, 52.1 ± 11.2 ml) were significantly less than those of the VATS radical resection group (128 ± 35.5 min, 217.9 ± 87.1 ml). Neither groups had postoperative death. The overall and tumor-free survival rate of the VATS wedge resection group within three years were 66.7% and 60.0%, and those of the VATS radical resection group were 93.8% and 94.1%, without significant difference (P > 0.05). The recurrence rates of the VATS wedge resection group and VATS radical resection group were 14.3% and 3.0%, without significant difference (P > 0.05).
It is safe, minimally invasive and meaningful to perform VATS wedge resection on the elderly high-risk patients with stage I PNSCLC.
PMCID: PMC3896765  PMID: 24359930
Elderly; Early lung cancer; Thoracoscope
17.  NADPH oxidase modulates MHC class II antigen presentation by B cells 
Phagocyte NADPH oxidase plays a key role in pathogen clearance via reactive oxygen species (ROS) production. Defects in oxidase function result in chronic granulomatous disease (CGD) with hallmark recurrent microbial infections and inflammation. The oxidase′s role in the adaptive immune response is not well-understood. Class II presentation of cytoplasmic and exogenous Ag to CD4+ T cells was impaired in human B cells with reduced oxidase p40phox subunit expression. Naturally arising mutations which compromise p40phox function in a CGD patient also perturbed class II Ag presentation and intracellular ROS production. Reconstitution of patient B cells with wild-type, but not a mutant, p40phox allele restored exogenous Ag presentation and intracellular ROS generation. Remarkably, class II presentation of epitopes from membrane Ag was robust in p40phox-deficient B cells. These studies reveal a role for NADPH oxidase and p40phox in skewing epitope selection and T cell recognition of self Ag.
PMCID: PMC3466399  PMID: 22984083
Human B cells; MHC class II presentation; NADPH oxidase
18.  Four Common Vascular Endothelial Growth Factor Polymorphisms (−2578C>A, −460C>T, +936C>T, and +405G>C) in Susceptibility to Lung Cancer: A Meta-Analysis 
PLoS ONE  2013;8(10):e75123.
Background and Objective
Vascular endothelial growth factor (VEGF) is one of the key initiators and regulators of angiogenesis and it plays a vital role in the onset and development of malignancy. The association between VEGF gene polymorphisms and lung cancer risk has been extensively studied in recent years, but currently available results remain controversial or ambiguous. The aim of this meta-analysis is to investigate the associations between four common VEGF polymorphisms (i.e., −2578C>A, −460C>T, +936C>T and +405C>G) and lung cancer risk.
A comprehensive search was conducted to identify all eligible studies to estimate the association between VEGF polymorphisms and lung cancer risk. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of this association.
A total of 14 published case-control studies with 4,664 cases and 4,571 control subjects were identified. Our meta-analysis provides strong evidence that VEGF −2578C>A polymorphism is capable of increasing lung cancer susceptibility, especially among smokers and lung squamous cell carcinoma (SCC) patients. Additionally, for +936C>T polymorphism, increased lung cancer susceptibility was only observed among lung adenocarcinoma patients. In contrast, VEGF −460C>T polymorphism may be a protective factor among nonsmokers and SCC patients. Nevertheless, we did not find any association between +405C>G polymorphism and lung cancer risk, even when the groups were stratified by ethnicity, smoking status or histological type.
This meta-analysis recommends more investigations into the relationship between −2578C>A and −460C>T lung cancer risks. More detailed and well-designed studies should be conducted to identify the causal variants and the underlying mechanisms of the possible associations.
PMCID: PMC3788083  PMID: 24098368
19.  SOD mRNA and MDA Expression in Rectus Femoris Muscle of Rats with Different Eccentric Exercise Programs and Time Points 
PLoS ONE  2013;8(9):e73634.
Although superoxide dismutase (SOD) and malondialdehyde (MDA) affect Delayed Onset Muscle Soreness (DOMS), their effects are unclear in rectus femoris muscles (RFM) of rats with different eccentric exercise programs and time points. The purpose of this study is to investigate the effects of the various eccentric exercise programs at different time points on the SOD mRNA expression and MDA using rat as the animal model.
248 male rats were randomly divided into 4 groups: control group (CTL, n = 8), once-only exercise group (OEG, n = 80), continuous exercise group (CEG, n = 80), and intermittent exercise group (IEG, n = 80). Each exercise group was divided into 10 subgroups that exercised 0.5 h, 6 h, 12 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, or 168 h. Rats were sacrificed and their SOD mRNA expression, and MDA concentrations of skeletal muscle tissue were measured.
The specimen in all eccentric exercise programs showed increased RFM SOD1 mRNA expression levels at 0.5 h (P<0.05), and decreased RFM SOD3 mRNA expression at 0.5 h (P<0.05). The continuous eccentric exercise (CE) significantly enhanced muscle SOD2 mRNA level at 0.5 h (P<0.05). After once-only eccentric exercise (OE), SOD1, SOD2, and SOD3 mRNA expression significantly increased at 96 h, whereas MDA concentrations decreased at 96 h. After CE, the correlation coefficients of SOD1, SOD2, SOD3 mRNA expression levels and MDA concentrations were −0.814, −0.763, −0.845 (all P<0.05) at 12 h.
Regular eccentric exercise, especially CE could enhance SOD1 and SOD2 mRNA expression in acute stage and the SOD2 mRNA expression correlates to MDA concentration in vivo, which may improve the oxidative adaption ability of skeletal muscles.
PMCID: PMC3772806  PMID: 24058480
20.  Shear Wave Speed Measurement Using an Unfocused Ultrasound Beam 
Ultrasound in medicine & biology  2012;38(9):1646-1655.
Tissue elasticity is related to pathology and therefore has important medical applications. Radiation force from a focused ultrasound beam has been used to produce shear waves in tissues for shear wave speed and tissue elasticity measurements. The feasibility of shear wave speed measurement using radiation force for an unfocused ultrasound beam is demonstrated in this study with a linear and a curved array transducer. Consistent measurement of shear wave speed was achieved over a relatively long axial extent (z = 10-40 mm for the linear array, and z = 15-60 mm for the curved array) in 3 calibrated phantoms with different shear moduli. In vivo measurements on the biceps of a healthy volunteer show consistent increase of shear wave speed for the biceps under 0, 1, 2, and 3 kg loading. Advantages and limitations of unfocused push are discussed.
PMCID: PMC3413738  PMID: 22766123
Elasticity; Shear wave; Ultrasound radiation force; Unfocused
21.  Comb-push Ultrasound Shear Elastography (CUSE): A Novel Method for Two-dimensional Shear Elasticity Imaging of Soft Tissues 
IEEE transactions on medical imaging  2012;31(9):1821-1832.
Fast and accurate tissue elasticity imaging is essential in studying dynamic tissue mechanical properties. Various ultrasound shear elasticity imaging techniques have been developed in the last two decades. However, to reconstruct a full field-of-view 2D shear elasticity map, multiple data acquisitions are typically required. In this paper, a novel shear elasticity imaging technique, comb-push ultrasound shear elastography (CUSE), is introduced in which only one rapid data acquisition (less than 35 ms) is needed to reconstruct a full field-of-view 2D shear wave speed map (40 mm × 38 mm). Multiple unfocused ultrasound beams arranged in a comb pattern (comb-push) are used to generate shear waves. A directional filter is then applied upon the shear wave field to extract the left-to-right (LR) and right-to-left (RL) propagating shear waves. Local shear wave speed is recovered using a time-of-flight method based on both LR and RL waves. Finally a 2D shear wave speed map is reconstructed by combining the LR and RL speed maps. Smooth and accurate shear wave speed maps are reconstructed using the proposed CUSE method in two calibrated homogeneous phantoms with different moduli. Inclusion phantom experiments demonstrate that CUSE is capable of providing good contrast (contrast-to-noise-ratio ≥ 25 dB) between the inclusion and background without artifacts and is insensitive to inclusion positions. Safety measurements demonstrate that all regulated parameters of the ultrasound output level used in CUSE sequence are well below the FDA limits for diagnostic ultrasound.
PMCID: PMC3475422  PMID: 22736690
comb-push; unfocused ultrasound beam; ultrasound elastography; acoustic radiation force; inclusion
22.  Identification of candidate genes for lung cancer somatic mutation test kits 
Genetics and Molecular Biology  2013;36(3):455-464.
Over the past three decades, mortality from lung cancer has sharply and continuously increased in China, ascending to the first cause of death among all types of cancer. The ability to identify the actual sequence of gene mutations may help doctors determine which mutations lead to precancerous lesions and which produce invasive carcinomas, especially using next-generation sequencing (NGS) technology. In this study, we analyzed the latest lung cancer data in the COSMIC database, in order to find genomic “hotspots” that are frequently mutated in human lung cancer genomes. The results revealed that the most frequently mutated lung cancer genes are EGFR, KRAS and TP53. In recent years, EGFR and KRAS lung cancer test kits have been utilized for detecting lung cancer patients, but they presented many disadvantages, as they proved to be of low sensitivity, labor-intensive and time-consuming. In this study, we constructed a more complete catalogue of lung cancer mutation events including 145 mutated genes. With the genes of this list it may be feasible to develop a NGS kit for lung cancer mutation detection.
PMCID: PMC3795175  PMID: 24130455
Lung cancer; Next-generation sequencing; Somatic mutation kit; COSMIC
23.  Comparative Quantitative Analysis of Gene Expression Profiles of Glycoside Hydrolase Family 10 Xylanases in the Sheep Rumen during a Feeding Cycle 
Xylanase is a crucial hydrolytic enzyme that degrades plant polysaccharides in the rumen. To date, there is no information on the genetic composition and expression characteristics of ruminal xylanase during feeding cycles of ruminants. Here, the major xylanase of the glycoside hydrolase family 10 (GH 10) from the rumen of small-tail Han sheep was investigated during a feeding cycle. We identified 44 distinct GH 10 xylanase gene fragments at both the genomic and transcriptional levels. Comparison of their relative abundance showed that results from the evaluation of functional genes at the transcriptional level are more reliable indicators for understanding fluctuations in xylanase levels. The expression patterns of six xylanase genes, detected at all time points of the feeding cycle, were investigated; we observed a complex trend of gene expression over 24 h, revealing the dynamic expression of xylanases in the rumen. Further correlation analysis indicated that the rumen is a dynamic ecosystem where the transcript profiles of xylanase genes are closely related to ruminal conditions, especially rumen pH and bacterial population. Given the huge diversity and changing composition of enzymes over the entire rumen, this research provides valuable information for understanding the role of functional genes in the digestion of plant material.
PMCID: PMC3568598  PMID: 23220966
24.  Video-assisted thoracoscopic surgery versus robotic-assisted thoracoscopic surgery in the surgical treatment of Masaoka stage I thymoma 
The purpose of this study was to compare perioperative outcomes in patients who underwent video-assisted thoracoscopic surgery or robot-assisted thoracoscopic surgery and assess the feasibility of robotic-assisted thymectomy for the treatment of Masaoka stage I.
We evaluated the short-term outcomes of 46 patients who underwent surgery for Masaoka stage I thymoma without myasthenia gravis between January 2009 and June 2012. Of these patients, 25 received unilateral video-assisted thoracoscopic surgery (VATS group) and the rest 21 recieved unilateral robotic-assisted thoracoscopic surgery (RATS group). We evaluated the duration of surgery, amount of intraoperative blood loss, duration of chest drainage, duration of postoperative hospital stay, hospitalization costs, postoperative complications and oncological outcomes.
The duration of surgery was not significantly different between the two groups. Intraoperative blood loss volumes did not differ significantly between the VATS and RATS groups (86.8 mL and 58.6 mL, respectively; P=0.168). The postoperative hospital stay was significantly shorter in the RATS group (3.7 days vs. 6.7 days; P <0.01), and the postoperative pleural drainage volume of the RATS group was significantly less than VATS group (1.1 days vs. 3.6 days; P <0.01). No patients in the RATS group needed conversion to open surgery. However, in the VATS series, one patient had conversion to an open procedure. No surgical complications were observed except that one case had pulmonary atelectasis in the RATS group and one case developed pneumonia after surgery. Use of robot is much more expensive than video. No early recurrence was observed in both groups.
Robotic thymectomy is feasible and safe for Masaoka stage I thymoma. RATS is equally minimally invasive as VATS and results in a shorter drainage period and reduced hospital stay compared with the VATS approach.
PMCID: PMC3716986  PMID: 23870330
Robotics; Thymoma; Minimally invasive surgery; Thymus
25.  Distinctive effects of T cell subsets in neuronal injury induced by co-cultured splenocytes in vitro and by in vivo stroke in mice 
Background and purpose
T cells and their subsets modulate ischemic brain injury. We studied the effects of the absence of T cell subsets on brain infarction after in vivo stroke and then used an in vitro co-culture system of splenocytes and neurons to further identify the roles of T cell subsets in neuronal death.
Stroke was induced by MCA suture occlusion in mice and infarct sizes were measured 2 days post-stroke.
Splenocytes were co-cultured with neurons, and neuronal survival was measured 3 days later.
A deficiency of both T and B cells (SCID) and the paucity of CD4 or CD8 T cells equally resulted in smaller infarct sizes as measured 2 days post-stroke. Although a functional deficiency of regulatory T cells had no effect, impaired Th1 immunity reduced infarction and impaired Th2 immunity aggravated brain injury, which may be due to an inhibited and enhanced inflammatory response in mice deficient in Th1 and Th2 immunity, respectively. In the in vitro co-culture system, WT splenocytes resulted in dose-dependent neuronal death. The neurotoxicity of splenocytes from the above immunodeficient mice was consistent with their effects on stroke in vivo , except for the mice with the paucity of CD4 or CD8 T cells, which did not alter the ratio of neuronal death.
T cell subsets play critical roles in brain injury induced by stroke. The detrimental versus beneficial effects of Th1 cells and Th2 cells both in vivo and in vitro reveal differential therapeutic target strategies for stroke treatment.
PMCID: PMC3506376  PMID: 22678086
cerebral ischemia; stroke; T cells; Th1; Th2

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