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Objective To explore the application value of breast cancer tumor markers tissue polypeptide specific antigen (TPS), carbohydrate antigen 15-3 (CA15-3), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) detection alone or in combination for the monitoring of distant metastasis of breast cancer. Method The clinical data of 389 female breast cancer patients admitted to Tianjin Medical University Cancer Institute and Hospital from January 2016 to March 2017 were retrospectively analyzed. Serum levels of TPS, CA125, CA15-3, and CEA were compared to analyze their significance in prediction distant metastasis of breast cancer. The patients were divided into the distant metastatic group and the non-metastatic group according to whether the patients had distant metastasis. The non-metastatic group was divided into the control group and the occult metastasis group according to whether distant metastases occurred in 3 years after treatment. Result The receiver operating characteristic curve analysis revealed that all four markers had the diagnostic value in distant metastasis of breast cancer (AUCTPS = 0.754, AUC15-3 = 0.821, AUCCEA = 0.755, AUCCA125 = 0.651) and in occult metastasis in 3 years after treatment (AUCTPS = 0.751, AUC15-3 = 0.744, AUCCEA = 0.725, AUCCA125 = 0.661). To estimate whether the discrimination ability could be improved by marker panels, we established marker panels composed of TPS, CA125, CA15-3, and CEA. To discriminate distant metastasis from non-distant metastasis, the diagnostic ability of different panels composed of TPS, CA125, CA15-3 and CEA did not show significant difference compared with single CA15-3 (P > 0.05). To discriminate occult metastasis from the control group, no significant difference was shown in AUC between marker panels and single marker (P > 0.05). However, the sensitivity was improved when the marker-panels were used overall. Conclusion All tumor markers have abilities in prediction of distant metastasis of breast cancer. The combined detection of the markers is more valuable than using single tumor marker in improving sensitivity. Two markers' panels are more suitable for the prediction of distant metastasis of breast cancer than three or four makers' panels with the similar sensitivity and AUC.

Background To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting. Methods This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity. Results The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.67–23.33] vs. 11.70 months [95% CI, 10.81–12.59], p p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). Conclusions Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.

Background Childhood overweight and obesity (OWO) has become a major public concern worldwide including in Shanghai, one of the most developed areas of China. Understanding perceptions and challenges of tackling childhood OWO among caregivers of children is critical to provide services in need. Methods A qualitative descriptive study including in-depth interviews with seven parents and six focus group discussions with a total of 32 parents or grandparents of children zero to 6 years of age. Participants lived in three districts of Shanghai and indexed children included both those with OWO or non-OWO children. Data were analyzed using qualitative thematic analysis. Results Caregivers tended to underestimate children’s weight status, and to regard chubby children as a sign of good parental care. Some caregivers even suggested that there were positive effects of childhood overweight. Caregivers identified a number of challenges to prevention of OWO in children, including difficulties in controlling dietary intake or increasing children’s physical activities; discordant views between parents and grandparents, and barriers to accessing professional guidance. Caregivers desired more detailed advice regarding children’s nutrition intake and physical activity, and preferred online approaches. Conclusions Misconceptions regarding childhood overweight were found in caregivers of children in Shanghai. Professional guidance on childhood weight control for caregivers is desired via digital applications such as mobile phone applications and social media.

Clinical research data show that gefitinib greatly improves the progression‐free survival of patients, so it is used in advanced non‐small cell lung cancer patients with EGFR mutation. However, some patients with EGFR sensitive mutations do not have good effects on initial gefitinib treatment, and this mechanism is rarely studied. METTL3, a part of N6‐adenosine‐methyltransferase, has been reported to play an important role in a variety of tumours. In this study, we found that METTL3 is up‐regulated in gefitinib‐resistant tissues compared to gefitinib‐sensitive tissues. Cell function experiments have proved that under the treatment of gefitinib, METTL3 knockdown promotes apoptosis and inhibits proliferation of lung cancer cells. Mechanistic studies have shown that METTL3 combines with MET and causes the PI3K/AKT signalling pathway to be manipulated, which affects the sensitivity of lung cancer cells to gefitinib. Therefore, our research shows that METTL3 can be used as a molecular marker to predict the efficacy of EGFR‐TKI therapy in patients, and METTL3 may be a potential therapeutic target.

Objectives Pancreatic cancer (PC) is a highly malignant tumor with poor detection sensitivity and specificity in biomarkers and diagnosis. Previous research indicated that serum Ephrin type-A receptor 2 in exosomes (Exo-EphA2) was highly expressed and might have facilitated cell migration in PC cells. However, the dynamics of clinical performance of serum Exo-EphA2 in PC patients are unknown. Thus, this study evaluated serum Exo-EphA2 as a potential diagnostic biomarker in PC. Methods The expressions of serum Exo-EphA2 were assessed by enzyme-linked immunosorbent assay for N = 353 serum samples, including from 204 PC patients, 75 patients with benign pancreatic disease, and 74 healthy control patients. Carbohydrate antigen 19-9 (CA 19-9) and carbohydrate antigen 242 (CA 242) were measured by automated immunoassay. Results Serum Exo-EphA2 levels were significantly higher in PC patients than in benign pancreatic disease and healthy control patients. Receiver operating characteristic curve analysis suggested that using combined diagnoses of Exo-EphA2 with CA 19-9 and CA 242 was more effective to discriminate early stage (stage I and II) in PC than in healthy controls and benign disease patients. Conclusions Novel findings suggest that serum Exo-EphA2 is a potential early diagnostic biomarker complementing CA 19-9 and CA 242 in PC.

Background: Postoperative cognitive dysfunction (POCD) is a general complication following cardiac and major non-cardiac surgery amongst the elderly, yet its causes and mechanisms are still unknown. The present study aimed to detect whether regional cerebral blood flow (CBF) is altered in the brain before surgery in POCD patients compared with non-POCD (NPOCD) patients, thus, CBF variation may potentially predict the occurrence of early POCD.Methods: Fifty patients scheduled for spinal stenosis surgery were enrolled in the study. All study participants completed a battery of neuropsychological tests (NPTs) by a well-trained neuropsychologist before the surgery and 1 week after the surgery. POCD was defined when the preoperative to postoperative difference of at least two of the NPTs’ |Z|-scores with reference to a control group exceeded 1.96. Pulsed arterial spin-labeling (ASL) MRI was scanned at least 1 day before surgery. The ASLtbx toolkit and SPM12 were applied to preprocess and correct the images, which were then normalized to the MNI brain template space to obtain standardized cerebral perfusion images.Results: POCD was identified in 11 out of 50 patients (22%). The CBF of the right superior temporal lobe, right and left middle cingulate gyrus, and the right hippocampus, and parahippocampal gyrus in POCD group was lower than that in NPOCD group (P < 0.001). The CBF of the pars triangularis of inferior frontal gyrus in POCD group was higher than that in NPOCD group (P < 0.001).Conclusions: These preliminary findings suggest that CBF premorbid alterations may happen in cognitively intact elderly patients that develop early POCD. Alterations of preoperative CBF might be a bio-marker for early POCD that can be detected by noninvasive MRI scans.

Background The incidence of brain metastasis (BM) in patients suffering from lung squamous cell carcinoma (LUSC) is lower than that in patients suffering from non-squamous cell carcinoma (NSCC) and there are few studies on BM of LUSC. The purpose of this investigation was to ascertain the risk factors of LUSC, as well as to establish a nomogram prognostic model to predict the incidence of BM in patients with LUSC. Methods Patients diagnosed with LUSC between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database and the patient data were collated. All patients diagnosed from 2010-2012 were allocated into the training cohort, and the remaining patients diagnosed from 2013-2015 formed the test cohort. Using factors that were screened out through logistic regression analyses, the nomogram in the training cohort was established. It was then evaluated for discrimination and calibration using the test cohort. The performance of the nomogram was assessed by quantifying the area under the receiver operating characteristic (ROC) curve and evaluating the calibration curve. Results A total of 26,154 LUSC patients were included in the study. The training cohort consisted of 16,543 patients and there were 8611 patients in the test cohort. Age, marital status, insurance status, histological grade, tumor location, laterality, stage of the cancer, number of metastatic organs, chemotherapy, surgery, and radiotherapy were highly correlated with the incidence of BM. The area under the ROC curve (AUC) of the nomogram for the training cohort and the test cohort were 0.810 [95% confidence interval (CI): 0.796 to 0.823] and 0.805 (95% CI: 0.784 to 0.825), respectively. The slope of the calibration curve was close to 1. Conclusions The nomogram was able to accurately predict the incidence of BM. This may be beneficial for the early identification of high-risk LUSC patients and the establishment of individualized treatments.

Making full use of the remaining oil-gas resources is a practical and feasible way to solve the problem of oil shortage. And the most important step of this method is the accurate detection of stratigraphic interface. In this paper, we propose a Convolutional Neural Network (CNN) approach for stratigraphic interface detection from the geophysical well logging data. Our proposed approach can automatically extract representative features from well logs data. It can reduce errors caused by human factors such as manual randomness and lack of experience. First of all, we normalize the data in the form of a single point of the well logging data and convert data points to 2D segment. We then feed segments into the CNN model for training. Secondly, we predict the formation of the well logging data using the trained model. Finally, we introduce a post-processing method to perform the stratigraphic interface detection. The experimental results demonstrate the proposed approach is able to achieve \(89.69\%\) of the average accuracy of stratigraphic interface detection. Moreover, the relative error between the predicted boundary points with the ground-truth is only \(1\%\), which indicates the proposed approach satisfy the real-world application requirements.

Face recognition (FR) technology is permeating and changing our lives from mobile phone to public space in China. Baidu utilizes advanced FR technology to support tens of thousands of employees in their daily access and payments. However, as a new way of human–machine interaction, a handful of researches of face interaction in the field of HCI were conducted. This study aimed to solve three issues: Users’ behavior during face interaction; What are the reasons for using and not using FR? What are the advantages of user experience of FR? With the methodology of field observation and interviews, we studied the face interaction on five typical scenarios, including the gate barriers, corridors, canteen, supermarket, and vending machines. Through the analysis of these issues, we had a comprehensive and in-depth understanding of experience problems and advantages of face interaction in public space. Basing on our findings, design implications were given focusing on reducing or avoiding these problems, and strengthen the advantages of face interaction. We believe it would be beneficial for the FR which is at the early stage of HCI research.

TV, as an important entertainment appliance in family, its interaction is typical of other screen-equipped devices. Far-field speech and mid-air gesture are the new trends in smart TV interaction. Previous studies have explored the characteristics of far-field speech and mid-air gesture interactions in TV used scenes, but rarely studied the user experience in the interaction process for the two interactive modes and directly compared them. What is the ideal interactive mode for TV in the future when these two can be realized? We know very little about this. Therefore, in Study 1, we quantitatively compared the user experience of far-field speech and mid-air gesture through experiment. The results showed that there were no significant differences between the two interactive modes, and implicated their advantages and disadvantages for different operations. And then, in study 2, we explored the user preference for interaction in different operations. The results showed that there were certain regularities about the participants’ preference for the two interaction channel in different situations. Based on the results mentioned above, we finally proposed the design principles of multichannel interaction fusion for different operations.

Fully homomorphic encryption (FHE) is a technique enabling processing to be performed directly on encrypted data in a commercial cloud environment, thereby preserving privacy. Large integer multiplication is the most time-consuming operation during the FHE. Concerning this issue, this paper proposes an operands merging method of the number theoretic transform (NTT) multiplication butterfly unit. By using the operands merging method and a fast modulo method, the operands of the radix-16 units are reduced to 43.8%. The hardware architecture of the NTT radix-16 unit is designed and implemented. The proposed design has been synthesized using 90-nm process technology and Xilinx Kintex UltraScale+ FPGA. The results show that the maximum frequency of the circuit is 600 MHz at the cost of 243k gates and 144 mW and 430 MHz at the cost of 19.6k CLB LUTs, 11.5k CLB registers, and 1.2k CARRY8 respectively. The multiplier implementation results also show that the optimization methods improve the area requirements and performance.

Tight sandstone gas from coal-measure source rock is widespread in China, and it is represented by the Xujiahe Formation of the Sichuan Basin and the Upper Paleozoic of the Ordos Basin. It is affected by planar evaporative hydrocarbon expulsion of coal-measure source rock and the gentle structural background; hydrodynamics and buoyancy play a limited role in the gas migration-accumulation in tight sandstone. Under the conditions of low permeability and speed, non-Darcy flow is quite apparent, it gives rise to gas-water mixed gas zone. In the gas displacing water experiment, the shape of percolation flow curve is mainly influenced by core permeability. The lower the permeability, the higher the starting pressure gradient as well as the more evident the non-Darcy phenomenon will be. In the gas displacing water experiment of tight sandstone, the maximum gas saturation of the core is generally less than 50% (ranging from 30% to 40% and averaging at 38%); it is similar to the actual gas saturation of the gas zone in the subsurface core. The gas saturation and permeability of the core have a logarithm correlation with a correlation coefficient of 0.8915. In the single-phase flow of tight sandstone gas, low-velocity non-Darcy percolation is apparent; the initial flow velocity (Vd) exists due to the slippage effect of gas flow. The shape of percolation flow curve of a single-phase gas is primarily controlled by core permeability and confining pressure; the lower the permeability or the higher the confining pressure, the higher the starting pressure (0.02–0.08 MPa/cm), whereas, the higher the quasi-initial flow speed, the longer the nonlinear section and the more obvious the non-Darcy flow will be. The tight sandstone gas seepage mechanism study shows that the lower the reservoir permeability, the higher the starting pressure and the slower the flow velocity will be, this results in the low efficiency of natural gas migration and accumulation as well as low gas saturation. The laboratory modeling on gas migration accumulation mechanism in coal-measure tight sandstone can provide a theoretic foundation to reveal the tight sandstone gas enrichment regularity, evaluation of prospecting area, and the study of development mechanism.

Background We conducted a systematic review and meta-analysis on drug-resistant tuberculosis in China to provide useful data for tuberculosis (TB) surveillance and treatment. Methods Several databases, including PubMed, Embase, and the Chinese Biological Medical Database, were systematically searched between January 1, 1999, and August 31, 2015, using strict inclusion and exclusion criteria. Results The corresponding drug-resistant TB prevalence between the new and previously treated cases was significantly different in almost all of the economic regions. The Eastern coastal region is the most developed economic region with the lowest total drug-resistant TB prevalence (any drug resistance: 28%; 95% confidence interval [CI], 25%-32%; multidrug resistance: 9%; 95% CI, 8%-12%) and the lowest number of new cases (any drug resistance: 21%; 95% CI, 19%-23%; multidrug resistance: 4%; 95% CI, 3%-5%). The Northwest is the least developed area with the lowest drug-resistant TB prevalence for previously treated cases (any drug resistance: 45%; 95% CI, 36%-55%; multidrug resistance: 17%; 95% CI, 11%-26%). The prevalence (multidrug and first-line drug resistance) exhibited a downward trend from 1996-2014. The extensively drug-resistant prevalence in China was 3% (95% CI, 2%-5%) in this review. Conclusions Overall, the status of drug-resistant tuberculosis in China is notably grim and exhibits regional epidemiologic characteristics. We are in urgent need of several comprehensive and effective control efforts to reverse this situation.

Nonrigid registration of multimodal medical images remains a challenge in image-guided interventions. A common approach is to use mutual information (MI), which is robust to the intensity variations across modalities. However, primarily based on intensity distribution, MI does not take into account of underlying spatial and structural information of the images, which might lead to local optimization. To address such a challenge, this paper proposes a two-stage multimodal nonrigid registration scheme with joint structural information and local entropy. In our two-stage multimodal nonrigid registration scheme, both the reference image and floating image are firstly converted to a common space. A unified representation in the common space for the images is constructed by fusing the structure tensor (ST) trace with the local entropy (LE). Through the representation that reflects its geometry uniformly across modalities, the complicated deformation field is estimated using $$L_{1}$$ or $$L_{2}$$ distance. We compared our approach to four other methods: (1) the method using LE, (2) the method using ST, (3) the method using spatially weighted LE and (4) the conventional MI-based method. Quantitative evaluations on 80 multimodal image pairs of different organs including 50 pairs of MR images with artificial deformations, 20 pairs of medical brain MR images and 10 pairs of breast images showed that our proposed method outperformed the comparison methods. Student’s t test demonstrated that our method achieved statistically significant improvement on registration accuracy. The two-stage registration with joint ST and LE outperformed the conventional MI-based method for multimodal images. Both the ST and the LE contributed to the improved registration accuracy.

There have been obstacles for internal migrants in China in accessing local public health services for some time. This study aimed to estimate the utilization of local public health services and its determinants among internal migrants. Data were from the 2014 and 2015 nationally representative cross-sectional survey of internal migrants in China. Multivariate logistic regressions were used to estimate the relationship between socioeconomic, migration, and demographic characteristics and public health services utilization. Our results showed that internal migrants in more developed eastern regions used less public health services. Those with higher socioeconomic status were more likely to use public health services. The years of living in the city of residence were positively associated with the utilization of public health services. Compared to migration within the city, migration across provinces significantly reduced the probability of using health records (OR = 0.88, 95% CI: 0.86-0.90), health education (OR = 0.97, 95% CI: 0.94-1.00), and health education on non-communicable diseases (OR = 0.92, 95% CI: 0.89-0.95) or through the Internet (OR = 0.96, 95% CI: 0.94-0.99). This study concludes that public health services coverage for internal migrants has seen great improvement due to government subsidies. Internal migrants with lower socioeconomic status and across provinces need to be targeted. More attention should be given to the local government in the developed eastern regions in order to narrow the regional gaps.

Among Chinese netizens, young women account for a relatively high percentage and become active users. As living standard improves, their focus have changed from the basic needs of life to the improvement of the quality of life and happiness, especially spending a lot of time on interest developing. Some Internet giants and many online educational institutions have paid attention to it, and released a number of online education products for young women to develop interests. In this research, we defined “Young women” in China and “Interest Developing” according to available data. We performed a detailed analysis in the group of “young women”, including their demographic characteristics, living styles, needs on interest developing, and specific learning processes. Then we took Baidu’s product for young women as an example, in comparison with other products on the Chinese market, to explore the design concepts, design style and operational activities of online interest-developing products. Finally, we summarized the strengths and weakness of existing products, and see what this industry is really achieving or how it’s trending. This research hopes to help design interest-developing products for Chinese young women, and even.

Targeted inhibition of Rho-associated kinase (ROCK)2 downregulates the proinflammatory T cell response while increasing the regulatory arm of the immune response in animals models of autoimmunity and Th17-skewing human cell culture in vitro. In this study, we report that oral administration of a selective ROCK2 inhibitor, KD025, reduces psoriasis area and severity index scores by 50% from baseline in 46% of patients with psoriasis vulgaris, and it decreases epidermal thickness as well as T cell infiltration in the skin. We observed significant reductions of IL-17 and IL-23, but not IL-6 and TNF-α, whereas IL-10 levels were increased in peripheral blood of clinical responders after 12 wk of treatment with KD025. Collectively, these data demonstrate that an orally available selective ROCK2 inhibitor downregulates the Th17-driven autoimmune response and improved clinical symptoms in psoriatic patients via a defined molecular mechanism that involves concurrent modulation of cytokines without deleterious impact on the rest of the immune system.

Background Calcineurin inhibitor–associated chronic nephrotoxicity threatens the prognosis of liver transplant recipients. This study aimed to study the mechanisms involved by identifying the cytokine profiles in tacrolimus (Tac)–induced nephrotoxicity. Methods We enrolled 125 living-donor liver transplant recipients. All of the recipients had normal serum cystatin (Cys) C and urine microalbumin before transplantation. They received a Tac-based immunosuppressive regimen (Tac + mycophenolate mofetil + prednisone) thereafter. Patients were grouped according to Cys-C results (measured a mean 3.55 ± 1.89 years after transplantation) as a measure of renal injury: the early renal damage group was Cys-C >1 mg/L, and normal renal function was Cys-C ≤1 mg/L. Serum levels of 10 cytokines and chemokines, as well as urine proteins including α1 microglobulin, microalbumin, transferrin, and immunoglobulin G, were compared between groups. Results In the early renal damage group, the concentration of interferon-γ–induced protein (IP) 10 was higher and monocyte chemotactic protein (MCP) 1 was lower compared with the group with normal renal function ( P = .027 and .048, respectively). Multivariate logarithmic regression analysis showed that IP-10 and MCP-1 were independently correlated with renal damage. Conclusions High level of IP-10 and low level of MCP-1 may be involved in renal injury and therefore may indicate poor prognosis. IP-10 could be a target for renal injury treatment after liver transplantation. Further studies with larger sample sizes are recommended to validate the study results.

Tuberculous meningitis continues to be a serious problem for physicians because it is difficult to make an early diagnosis and the consequences of delaying treatment are severe. The objective of this study is to provide data for the optimization of diagnostic and timely treatment of tuberculous meningitis. Of the 401 human immunodeficiency virus (HIV)-negative tuberculous meningitis patients in our study, 332 were found to have an impaired blood brain barrier (82.8%). Nearly 17.0% of patients failed to be timely diagnosed. Headache (53.6%) and fever (48.6%) were the most common features and Computed Tomography/Magnetic Resonance Imaging (CT/MRI) detected 96 patients (23.9%) with abnormal meningeal imaging. Cerebrospinal fluid real-time polymerase chain reaction was positive in 73.8% of the tuberculous meningitis patients, whereas, smears and cultures detected only 6.7% and 5.2%, respectively. Further analysis identified striking differences between drug-resistant and drug-susceptible tuberculous meningitis. Patients with drug resistance correlated with grave prognosis. Tuberculous meningitis diagnosis should overall embody clinical symptoms, laboratory and cerebral imaging findings and more sensitive diagnostic approaches are still warranted. Our data suggest cerebrospinal fluid polymerase chain reaction for mycobacterial DNA and molecular drug susceptibility testing as routine assays for suspected tuberculous meningitis patients and observation of the blood brain barrier function could be performed for individual management.

This study focuses on media literacy education in mainland China with a historical review, based on document analysis, and try clarifying the origins, conferences, higher education and press of media literacy education. We found that the development of media literacy education had to face difficulties and challenges. It could be listed as follows: basic principles of discipline should be clearly shown; low localization and lack of social support; uneven geographical distribution of educational resources; ignoring the role of family for media literacy education.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Conduction block in demyelinated axons underlies early neurological symptoms, but axonal transection and neuronal loss are believed to be responsible for more permanent chronic deficits. Several therapies are approved for treatment of relapsing-remitting MS, all of which are immunoregulatory and clinically proven to reduce the rate of lesion formation and exacerbation. However, existing approaches are only partially effective in preventing the onset of disability in MS patients, and novel treatments to protect myelin-producing oligodendrocytes and enhance myelin repair may improve long-term outcomes. Studies in vivo in genetically modified mice have assisted in the characterization of mechanisms underlying the generation of neuropathology in MS patients, and have identified potential avenues for oligodendrocyte protection and myelin repair. However, no treatments are yet approved that target these areas directly, and in addition, the relationship between demyelination and axonal transection in the lesions of the disease remain unclear. Here, we review translational research targeting oligodendrocyte protection and myelin repair in models of autoimmune demyelination, and their potential relevance as therapies in MS patients.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the brain and spinal cord with a presumed autoimmune etiology. Conduction block in demyelinated axons underlies early neurological symptoms, whereas axonal transection is believed responsible for more permanent later deficits. Approved treatments for the disease are immunoregulatory, and reduce the rate of lesion formation and clinical exacerbation, but are only partially effective in preventing the onset of disability in MS patients. Approaches that directly protect myelin-producing oligodendrocytes and enhance remyelination may improve long-term outcomes and reduce the rate of axonal transection. Studies in genetically modified animals have improved our understanding of mechanisms underlying CNS pathology in MS models, and have identified pathways that regulate oligodendrocyte viability and myelin repair. However, although clinical trials are ongoing, many have been unsuccessful and no treatments are yet approved that target these areas in MS. In this review, we examine avenues for oligodendrocyte protection and endogenous myelin repair in animal models of de- and remyelination, and their relevance as therapeutics in human patients.

While a substantial amount of data on gene mutations related to acute myeloid leukemia (AML) prognosis from western and other populations have been reported, these studies largely describe one or two genes. Additionally, in southwest China, only insufficient data exist regarding FLT3-ITD, FLT3-TKD, NPM1, C-KIT, DNMT3A, and CEBPA mutations have been widely used in clinical settings. Therefore, a comprehensive study about these mutations of clinical importance in the prognosis of AML in western China is necessary. In a cohort of 255 patients with de novo AML, we retrospectively analyzed the prevalence of the six gene mutations, and then we assessed the results in conjunction with clinical characteristics and treatment responses. As for the frequencies of these mutations, the NPM1 mutation occurred most frequently (17.7 %; 42/237), followed by the CEBPA mutation (15.0 %; 19/127) and the FLT3-ITD mutation (10.2 %; 25/244). The frequencies of the FLT3-TKD, DNMT3A, and C-KIT mutations were 3.7 % (9/234), 4.0 % (9/225) and 4.2 % (10/238), respectively. These mutations were closely related to clinical characteristics including FAB classification, gender and age, hemogram, blasts (%), fusion genes, and immunophenotypes. Additionally, a higher complete remission (CR) rate was found in NPM1-mutated patients. The occurrence of these mutations is variable among different countries and regions worldwide, which may provide clues to the etiology of AML. Besides, we identified new clinical characteristics that advance our understanding of these mutations and further clarify the involvement of these mutations in the development of leukemia.

Since the hypothesis that solid tumors cause angiogenesis by secreting pro-angiogenic factors was introduced, research on angiogenesis has proceeded continuously. Development of inhibitors targeting the angiogenic tyrosine kinases, to block downstream signal transduction pathways, has become an important approach to cancer therapy. Our goal was to study the development and mechanism of anti-angiogenic tyrosine kinases inhibitors. We researched data on discovery of the inhibitors and their binding modes using the PubMed, Web of Science, Food and Drug Administration (FDA), and Clinical Trials Web sites. In the last decade, many small molecule inhibitors targeting angiogenesis have been designed and synthesized with many now entering the clinic or gaining FDA approval. Advances in understanding regulatory mechanisms of angiogenesis have enabled development of these drugs. The development of inhibitors up to Phase 3 clinical trials and, for many, FDA approval has helped leading to the discovery of additional compounds. The structures, activities, and binding modes of these inhibitors are discussed in this review. Though the angiogenesis inhibitors have different chemical structures, they share similar binding modes. Their interactions with the hinge region of receptor tyrosine kinases (RTKs) are critical to their effectiveness as inhibitors. In addition, as we review here, different drugs, when bound, induce different conformations of RTKs.

The membrane separation technology used in Chinese medicine extracts, namely extracts microfiltration to remove suspended solids, and then to ultra-filtrate to remove impurities macromolecules. By compared microfiltration, ultra-filtration process of investigation with traditional alcohol precipitation process, this paper holds that the adoption of a membrane separation process has significant advantages.

This paper proposes an adaptive mesh refinement strategy for the finite element method (FEM) based elastic registration model. The signature matrix for mesh refinement takes into account the regional intensity variance and the local deformation displacement. The regional intensity variance reflects detailed information for improving registration accuracy and the deformation displacement fine-tunes the mesh refinement for a more efficient algorithm. The gradient flows of two different similarity metrics, the sum of the squared difference and the spatially encoded mutual information for the mono-modal and multi-modal registrations, are used to derive external forces to drive the model to the equilibrium state. We compared our approach to three other models: (1) the conventional multi-resolution FEM registration algorithm; (2) the FEM elastic method that uses variation information for mesh refinement; and (3) the robust block matching based registration. Comparisons among different methods in a dataset with 20 CT image pairs upon artificial deformation demonstrate that our registration method achieved significant improvement in accuracies. Experimental results in another dataset of 40 real medical image pairs for both mono-modal and multi-modal registrations also show that our model outperforms the other three models in its accuracy.

This paper proposes a novel nonrigid medical image registration algorithm based on the finite element elastic model. The deformation is constrained by the image external force and the landmark information while solving the optimization problem. We obtain the landmark information by means of automatically extracting the corresponding scale-invariant features from the reference image and float image. Meanwhile the gradient field of the image similarity metric is derived for the image external force. The qualitative and quantitative evaluations of our proposed method have been performed on both MR image pairs and mammographic images. The result of experiments shows that the algorithm of this paper improves the alignment between the reference image and float image.

Supplemental Digital Content is available in the text, Recent studies have proposed that the ASAP1 gene participates in regulating the adaptive immune response to Mycobacterium tuberculosis infection. A GWAS study has reported that ASAP1 polymorphisms (rs4733781 and rs10956514) were associated with the risk of tuberculosis (TB) in Russians. But due to population heterogeneity, different races would have different causative polymorphisms, and the aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) of the ASAP1 gene and TB risk in Chinese population. A total of 7 SNPs in the ASAP1 gene were genotyped in 1115 Western Chinese Han and 914 Tibetan population using an improved multiplex ligation detection reaction (iMLDR) method. The associations of SNPs with TB risk and clinical phenotypes were determined based on the distributions of allelic frequencies and different genetic models. A meta-analysis was carried out to further assess the relationship between ASAP1 polymorphism and TB risk. Statistical comparisons of cases and controls after correction for multiple testing did not yield any significant associations with the risk of TB via analyses of a single locus, haplotype, and subgroup differences. Meta-analysis showed no evidence supporting association between rs10956514 and overall risk for TB. Subsequent analysis referring to the genotypes of SNPs in relationship to clinical phenotypes identified that rs4236749 was associated with different serum C-reactive protein levels, suggesting a role of this locus in influencing the inflammatory state of Western Chinese Han patients with TB. Our present data revealed that ASAP1 polymorphisms are unlikely to confer susceptibility to TB in the Western Chinese Han and Tibetan populations, which challenges the promising roles of the ASAP1 gene in the development of TB and highlights the importance of validating the association findings across ethnicities.

Location has become a key service for smartphone applications. Nowadays, GPS and network-based technology have been widely used to provide location service. However, the former suffers its high power consumption, and the latter has some imperfections in location accuracy. In this paper, we present a reliable and energy-efficient localisation system using inertial sensors commonly found on today's smartphone. We first give an overall view of the localisation system, and then describe the key components separately. Furthermore, reliable algorithms for displacement determination and heading direction have been developed, and Vincenty's formulae are used to calculate the location of the endpoint. Location error correction mechanisms are also proposed to prevent accumulated error. Evaluation on Samsung I9100 in the real condition confirm anticipated benefits, and results show that ACMG uses 24.7% less power than GPS, and get a mean location accuracy of less than 6.7m in the playground of Nankai University.

Cognitive radio (CR) as one of the most promising technologies to solve the problem of exhausting of spectrum resource, draws a lot of attention recently. However, for the highly intelligent wireless devices in the future, the assumption "CR devices introduce no interference to the primary users (PUs)" in traditional CR systems may do not exist anymore, due to that the devices are always trying to maximize their own reward, without considering the interference to the others. In this paper, the concept of proactively-optimization CR network is introduced to deal with this problem by enforcing ``punishment'' or ``penalty'' to illegal CR transmissions. Under the framework of proactively-optimization CR networks, with the reward function defined in this paper, the spectrum resource allocation decision making problem of primary users is modeled as a Markov decision process (MDP), and an optimal resource allocation scheme with the objective of maximizing the PU's reward is proposed. Furthermore, extensive simulation results show that the proposed scheme improves the reward significantly compared to the existing scheme.

IEEE 802.11 wireless LAN, after the transmission of each beacon frame, there will be a large number of stations in power saving mode (PS mode, PSM) trying to send power saving poll (PS-Poll) frames to contend the right to receive the buffered downlink packets. However, excessive contention results in higher collision probability, higher power consumption and lower throughput than usual. To solve this problem, we propose a downlink access scheme which modifies the traffic indication map (TIM) fields in beacon frames to enhance the control ability of access point (AP). This scheme which can be used in both the basic access scheme and the access scheme with RTS/CTS enables AP to constrain the number of stations in contention to be an optimal number. Furthermore, the proposed MTIM scheme provides a convenient way for quality of service (QoS) differentiation by limiting the PS-Poll transmitting of stations with lower priority. Simulation results provided in this paper prove the performance improvement.

Objective: Laquinimod is an orally administered CNS-active immunomodulator currently in phase III clinical trials for therapy of relapsing remitting multiple sclerosis (RRMS). Data show that RRMS patients show beneficial effects of laquinimod 0.6mg on clinical disease activity as evidenced by slowing of the progression of disability, reducing the rate of MRI-measured brain volume loss, and reducing relapse rate. The current work examines the mechanisms underlying these effects. Background Laquinimod crosses the blood-brain barrier and enters the CNS, thus in addition to peripheral effects it may act directly on CNS-resident lineages including oligodendrocytes, microglia and astrocytes. Increasing evidence implicates reactive astrocytes as critical regulators of CNS inflammation and repair in MS. Design/Methods: Here, we report that laquinimod profoundly impacts proinflammatory gene expression in a human in vitro model of reactive astrogliosis. Results: Interleukin-1beta (IL-1β) is implicated in lesion pathogenesis in RRMS, and in primary human astrocyte cultures it strongly induced inflammatory factors including cytokines, chemokines and reactive nitrogen species. Importantly, at therapeutic concentrations, laquinimod abrogated IL-1β-induced induction of cytokines including tumor necrosis factor-α (TNFα) and IL-6, and inducible nitric oxide synthase. Laquinimod also differentially regulated IL-1β-induced expression of CXC and CC chemokines, suggesting that it acts as an immunomodulator rather than an immunosuppressant in astrocyte cultures. IL-1β exerts its effects via the transcription factor NF-κB, and suggesting mechanism, laquinimod pretreatment of human astrocytes downregulated NF-κB activation. Conclusions: Collectively, these data reveal laquinimod as a regulator of the proinflammatory phenotype in a human model of reactive astrogliosis, and suggest that it may act centrally on resident CNS cells to restrict pathology in MS lesions. Supported by: A research grant from Teva Pharmaceuticals. Disclosure: Dr. Pham has nothing to disclose. Dr. Zhang has nothing to disclose. Dr. Hayardeny Nisimov has nothing to disclose. Dr. John has received personal compensation for activities with EMD Serono, Teva Neuroscience, and Biogen Idec. Dr. John has received research support from Teva Neuroscience, and Vaccinex Inc.