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The Notch signaling pathway is related to endothelial dysfunction in coronary atherosclerosis. Our objective was to explore the role of Notch signaling in coronary microvascular dysfunction (CMD). CMD models were constructed by sodium laurate injection in vivo and homocysteine (Hcy) stimulation in vitro. The binding ability of Notch Intracellular Domain (NICD)/H3K9Ac/GCN5 (General Control Non-derepressible 5) to Neuregulin-1 (Nrg-1) promoter was examined by chromatin immunoprecipitation. Immunofluorescence staining was conducted to detect CD31 positive cells, NICD localization, and co-localization of NICD and GCN5. Flow cytometry and Tunel staining were conducted to identify the apoptosis. Hematoxylin and eosin staining, quantitative real-time PCR, western blot, immunohistochemical staining, co-immunoprecipitation, and double luciferase report analysis were also conducted. Notch signaling pathway-related protein levels were decreased, levels of Nrg-1 and the phosphorylation of ErbB2 and ErbB4 were enhanced in CMD models. Interference with Nrg-1 further increased the apoptosis in Hcy-induced cardiac microvascular endothelial cells (CMECs). Meanwhile, the activation of the Notch signaling pathway increased the levels of Nrg-1 and the phosphorylation of ErbB2 and ErbB4, as well as inhibited the apoptosis induced by Hcy. Furthermore, NICD and histone acetyltransferase enzyme GCN5 could regulate Nrg-1 promoter activity by affecting the expression of acetylation-modified protein H3K9Ac. In addition, NICD also interacted with GCN5. In vivo results also confirmed that the activation of the Notch signal alleviated CMD. Notch signaling pathway regulates Nrg-1 level through synergistic interaction with GCN5, thereby mitigating CMD.

The apoptosis and inflammation in cardiac microvascular endothelial cells (CMECs) promote the development of coronary microvascular dysfunction (CMD). The present study aimed to explore the role of E3 ubiquitin ligase mind bomb 1 (MIB1) in the apoptosis and inflammation in CMECs during CMD.In vivo, CMD in rats was induced by sodium laurate injection. In vitro, rat primary CMECs were stimulated by homocysteine (Hcy). The apoptosis of CMECs was measured using flow cytometry. The inflammation of CMECs was evaluated by the level of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β). The interplay between MIB1 and mitogen-activated protein kinase kinase kinase 5 (map3k5, also called ASK1) was measured using Co-immunoprecipitation.MIB1 expression was decreased and ASK1 expression was increased in the heart tissues of CMD rats and Hcy-treated CMECs. MIB1 overexpression decreased fibrinogen-like protein 2 (FGL2) secretion, inflammation, and apoptosis induced by Hcy in CMECs. Meanwhile, MIB1 overexpression decreased the protein levels of ASK1 and p38, while not affected ASK1 mRNA levels. The following mechanism experiments revealed that MIB1 downregulated ASK1 expression by increasing its ubiquitination. ASK1 overexpression reversed the inhibitory effect of MIB1 on FGL2 secretion, apoptosis, inflammation, and p38 activation in Hcy-treated CMECs. In CMD rats, MIB1 overexpression partly retarded CMD progression, manifesting as increased coronary capillary density and decreased microthrombi formation.MIB1 overexpression relieved apoptosis and inflammation of CMECs during CMD by targeting the ASK1/p38 pathway.

Flavanomarein (FM) is a major natural compound of Coreopsis tinctoria Nutt with protective effects against diabetic nephropathy (DN). In this study, we investigated the effects of FM on epithelial-mesenchymal transition (EMT) in high glucose (HG)-stimulated human proximal tubular epithelial cells (HK-2) and the underlying mechanisms, including both direct targets and downstream signal-related proteins. The influence of FM on EMT marker proteins was evaluated via western blot. Potential target proteins of FM were searched using Discovery Studio 2017 R2. Gene Ontology (GO) analysis was conducted to enrich the proteins within the protein-protein interaction (PPI) network for biological processes. Specific binding of FM to target proteins was examined via molecular dynamics and surface plasmon resonance analyses (SPR). FM promoted the proliferation of HK-2 cells stimulated with HG and inhibited EMT through the Syk/TGF-β1/Smad signaling pathway. Spleen tyrosine kinase (Syk) was predicted to be the most likely directly interacting protein with FM. Combined therapy with a Syk inhibitor and FM presents significant potential as an effective novel therapeutic strategy for DN.

The samples of MnOx/TiO2 catalysts supported on cordierite honeycomb ceramics were prepared by a sol-gel-impregnation method, and evaluated for low-temperature (353-473 K) selective catalytic reduction (SCR) of NOx with NH3. The influences of pretreatment on cordierite and catalyst dosage were investigated at first and optimized as follows: pickling for cordierite honeycomb ceramics with 1 mol/L HNO3 for 3 h prior to loading procedure as well as the catalyst dosage of 3-5 wt.%. The activity results indicated that there was an optimum working condition for MnOx/TiO2/cordierite catalysts: NH3/NO molar ratio=1.1, [O2]=3 vol.%, GHSV=5514 h-1, the highest activity of nearly 100% NO conversion could be obtained. As a comparison, the performances of commercialized vanadium-based honeycomb catalyst were also employed, which revealed the narrower scope of application of GHSV and the higher active temperature window. In conclusion, it turns out that the prepared MnOx/TiO2/cordierite catalysts are more applicable as a low-temperature SCR catalyst for NOx removal in a more complicated application environment.

A series of spherical-like MnOx/TiO2 catalysts with F-doped were prepared by using sol-gel method and investigated for low-temperature selective catalytic reduction (SCR) of NOx with NH3 at the temperature ranging from 100 °C to 200 °C. The 0.07Ce-MnOx/TiO2 catalyst shows the highest activity and yields 95% NO conversion at 200 °C. With the help of XRD, TGA, H2-TPR, NH3-TPD, BET and TEM, the structures and properties of the catalysts were characterized. The results show that it is a fine modifier for TiO2 support with appropriate amounts of F doping, and F ions can enter into TiO2 lattice, reducing the formation of rutile TiO2 and the crystallization of MnOx. However, MnTiO3 was generated in the catalysts with excess F doping. This would cause larger diameter of spherical particle and smaller surface area. But the amounts of the surface acid sites increased, and the reduction ability of catalysts was enhanced, which is beneficial for catalytic activity of the catalysts.

This paper analyzes the existing problems of acting lapping pressure in lapping internal holes of main cylinder of brake-pump with solid abrasives, proposes a new type of solid abrasives supporting method, namely, three supportting points acting lapping pressure method. The method improves pressure distribution between solid abrasives and the surface of the machined workpiece,which is favorable to increase cylindricity of machined hole.Through actual machining process, new method is demonstrated increasing cylindricity accuracy of machined holes of main cylinder significantly.

Background: Enterovirus 71 (EV71) is highly contagious and can cause severe complications. A safe and effective vaccine is needed. We assessed the reactogenicity and immunogenicity of an inactivated, alum-adjuvanted EV71 vaccine in this study. Methods: A randomized, double-blind, placebo-controlled clinical trial was undertaken in 360 healthy participants who were stratified into 2 age groups (6-12 and 13-60 months), and randomly allocated to receive placebo or the investigational vaccine containing 160 U, 320 U or 640 U antigen per dose by the ratio of 1: 1: 1: 1 at days 0 and 28. Reactogenic data within 28 days after each vaccination were recorded. Blood samples were obtained on days 0, 28 and 56 for neutralizing antibody assay. Results: Overall, 193 participants reported at least 1 injection-site or systemic adverse reaction with 53.3% and 54.4% participants receiving the study vaccine and placebo, respectively. Most of the reactions were mild or moderate. Three serious adverse events were observed, but none was related to vaccination. In the participants with seronegative baseline, after 2 doses all the participants receiving EV71 vaccines were seropositive and the seroconversion rates were more than 98.1%. In the participants with seropositive baseline, 1 dose induced good seroconversion rates of more than 64.3% in participants receiving EV71 vaccines. Conclusions: This study found that the inactivated EV71 vaccine was well tolerated and had good immunogenicity in healthy children and infants. A single dose induced typical booster response in the participants with a seropositive baseline, and 2 doses were needed for the immunologically naive participants.

In the APF system, PWM control plays an important role in improvement of power quality and harmonic compensation. Given the current PWM control method assumes DC voltage as constant. So the APF operating loss and energy exchange among system components cause the DC voltage the certain fluctuation which deteriorates the effect of harmonic compensation. This paper presents an improved PWM method which uses the designed fuzzy PID controller to control the deviation between the calculated voltage and the set one, adjust the size of the duty cycle to modify PWM waves, and make the output stability in the new set-point. Finally, it shows the simulation results in this paper. This improved PWM approach makes the AV output to avoid the influence from the DC fluctuation, and obtains the ideal harmonic compensation effect

Background and purpose To compare positional and volumetric differences of planning target volumes (PTVs) based on axial three-dimensional CT (3DCT) and four-dimensional CT (4DCT) for the primary tumor of non-small cell lung cancer (NSCLC). Materials and methods Twenty-eight patients with NSCLC underwent 3DCT and 4DCT scans of the thorax during normal free breathing. PTV vector was defined on 3DCT using the individual tumor motion vector measured by 4DCT accounting for tumor motion; PTV 4D was defined on all phases of 4DCT images. In addition, a 7mm margin for microscopic disease and a 3mm setup margin were used for above PTVs, respectively. The differences in target position, volume and coverage between PTV vector and PTV 4D were evaluated for tumors in different lobes, respectively. Results The median motion vector for tumors located in the upper lobe (group A) and in the middle lower lobe (group B) was 2.8 and 7mm, respectively. The mean centroid shifts between PTV vector and PTV 4D in the LR, AP and CC directions for group A and B were close to zero. The median size ratio of PTV 4D to PTV vector was 0.75 and 0.52 for group A and B. The motion vector showed a significant correlation to the ratio of PTV 4D to PTV vector for group A and B ( p =0.008 and 0.003). The median DI of PTV vector in PTV 4D was 69.19% for group A and 51.60% for group B. The median DI of PTV 4D in PTV vector was 98.99% for group A and 99.94% for group B. Conclusion It is necessary to expand the internal margin isotropically in a single direction for 3DCT treatment planning due to the uncertainty of the 3DCT-based target position. The 3DCT-based PTV using individual margins provides a good coverage of the 4DCT-based PTV, meanwhile encompasses relatively large normal tissues, especially for middle and lower lobe tumors. We should be cautious about the use of the individual PTV derived from 3DCT in treatment planning.

The aim was to demonstrate the immunogenicity and safety of a DTaP-IPV//PRP-T combined vaccine (Pentaxim ® ) compared to individual vaccines in infants in the People's Republic of China. Infants ( N = 792) were randomly assigned to receive DTaP-IPV//PRP-T at 2, 3 and 4 months of age (Group A) or 3, 4 and 5 months of age (Group B), or DTaP (Wuhan Institute of Biological Products), PRP-T (Act-Hib ® ) and IPV (Imovax ® Polio) at 3, 4 and 5 months of age (Group C). Antibody titers were measured pre- and 1 month after the third vaccination; non-inferiority analyses were performed for seroprotection/seroconversion (SP/SC) rates. Safety was assessed 1 month after the primary series. SP/SC rates for the DTaP-IPV//PRP-T vaccine were high and non-inferior to the controls. Reactogenicity was low for each group and no hypotonic hyporesponsive episode or seizure was reported. In conclusion, the DTaP-IPV//PRP-T vaccine was highly immunogenic, non-inferior to the commercially available control vaccines and had a good safety profile for both primary administration schedules.

The single radial immunodiffusion (SRID) method currently used to determine the hemagglutinin (HA) content of the inactivated influenza vaccines depends on the availability of reference HA antigen and corresponding anti-serum, updated and provided annually by World Health Organization (WHO) collaborative centers. Particularly early in a pandemic outbreak, reference reagents could be the bottleneck in vaccine development and release. Therefore, other reliable tests capable of quantifying HA content could substantially shorten the time needed for vaccine formulation. Here electrophoretic separation of deglycosylated samples in conjunction with densitometry was used to quantify HA contents of H1N1 vaccine at multiple manufacturing sites. We found the overall consistency between the alternative method and traditional SRID was 88-122% in seven lots of vaccine bulks from four subtypes (types) of influenza vaccine, confirming its suitability to quantify HA content. Moreover, we used the alternative method to prepare a national HA antigen reference in China for quality control of 2009 pandemic influenza A (H1N1) vaccines prior to the arrival of the WHO SRID reference standards, subsequently confirming good agreement between both methods. The alternative method for vaccine quantification enabled the Chinese health authority to approve H1N1 vaccine 1 month earlier than otherwise possible.

This paper presents an analytical study of local instability behavior in a reduced beam section (RBS) beam subjected to cyclic loading. A general finite-element method is used for numerical experiments here. Even though lateral instability in the RBS beam is prevented, strength deterioration may occur due to local buckling of the RBS portion. The writers suggest that stiffeners arranged in the RBS portion can delay the occurrence of local buckling. To address the possibility that reinforcement of the RBS portion might offset the advantage of RBS, the stress distribution of beam end of the RBS with stiffeners was compared to that of an RBS beam without stiffeners. Stiffening the RBS portion did not cause an excessive stress concentration. These analyses suggest that an RBS beam can be sufficiently strengthened by placing two stiffeners at the boundaries that divide the RBS portion into three equal regions and the stiffener thickness required is the same thickness as the web.

In the commercial test for smooth tube inserted with rotors-assembled strand comparing with non-inserted ones on condensers in electric power plant, using water as working fluid, the single-phase pressure drop and heat transfer were measured. It was found difficult to receive reliable and accurate enough data through commercial test. Meanwhile, the single-phase pressure drop and heat transfer in a rotors-assembled strand inserted tube were measured in laboratory, with the tube side Prandtl numbers varying from 5.67 to 5.80 and the tube side Reynolds numbers varying from 21,300 to 72,200. Before that, a validation experiment based on the same smooth tube was carried out to testify the experimental system and the data reduction method, in which fixed mounts were employed to eliminate entrance effects. The Prandtl numbers varied from 5.64 to 5.76 and the Reynolds numbers varied from 19,000 to 56,000 in the tube. The annular side Reynolds numbers remained nearly constant at the value of around 50,000 for all experiments, with the annular side Prandtl numbers varying from 8.02 to 8.22. The experimental results of smooth tube show that employment of fixed mounts leads to a visible bias of friction factor at relative low Reynolds numbers while it hardly affects the Nusselt numbers. On the other hand, experiment for the tube inserted with rotors-assembled strand show remarkable improvement for heat transfer with the Nusselt number increased by 9.764–11.87% and the overall heat transfer coefficient increased by 7.08–7.49% within the range of Reynolds number from about 21,300 to 55,500. Meanwhile, friction factor increases inevitably by 278.1–353.9% within the same range of Reynolds number. Based on through multivariant linear normal regression method, the Reynolds number and Prandtl number dependencies of the Nusselt number and friction factor were determined to be Nu = 0.0031 Re 0.9 Pr 1.0849 and f = 0.993 Re −0.22 .

A method for testing an air-spring was advanced in the beginning. Then ANSYS was utilized to simulate the static test. In the simulation, multiple load steps solution was carried out through APDL *DO-LOOP and array parameter method. Scalar parameter PRESSURE was established as inner pressure tracking parameter to update inner pressure. Table parameter PRESSURES was established as inner pressure output parameter to export inner pressure of each load step. Comparison was done between simulation result and test data to prove the feasibility of simulation. Finally, some major parameters such as cord angle and initial inner pressure were taken into account, which had remarkable effect on the air-spring’s performance.

To compare the position, displacement, degree of inclusion (DI) and matching index (MI) of the gross tumor volume (GTV) for peripheral lung cancer based on 4-dimensional CT (4D CT) and 3-dimensional CT (3D CT) assisted with active breathing control (ABC).Eighteen patients with peripheral lung cancer underwent 4D CT simulation scan during free breathing and 3D CT simulation scans in end-inspiratory hold (CTEIH) and end-expiratory hold (CTEEH) in turn. The 4D CT images from each respiratory cycle were sorted into 10 phases. phase 0 was defined as end-inspiratory phase (CT0), and phase 50 was defined as end-expiratory phase (CT50). The GTVs were delineated separately on CT0, CT50, CTEIH and CTEEH images, and then GTV0, GTV50, GTVEIH and GTVEEH were constructed, respectively.The median distances between the centroids of GTV0 and GTVEIH, GTV50 and GTVEEH were 3.9 mm and 3.4 mm in all patients, 3.2 mm and 3.1 mm in the upper lobe group, and 5.0 mm and 4.7 mm in the lower lobe group, respectively. In the upper lobe group, the GTV0 and GTVEIH were 65.9% and 63.1%, and the median mutual DIs of GTV50 and GTVEEH were 67.5%, 63.1%, respectively. In the lower lobe group, the GTV0 and GTVEIH were 35.3% and 21.4%, and the median mutual DIs of GTV50 and GTVEEH were 27.8% and 24.8%, respectively. In the upper lobe group, the median MI of GTV0 and GTVEIH was 0.5, and the median MI of GTV50 and GTVEEH was 0.6. In the lower lobe group, the median MI of GTV0 and GTVEIH was 0.2, and the median MI of GTV50 and GTVEEH was 0.3. Whether in the upper or lower lobe groups, all the differences between displacements of centroid positions of GTVEIH and GTVEEH (ABC displacement) and GTV0 and GTV50 (4D displacement ) were1 mm in three dimensional directions (all P0.05).The target displacement of tumors based on 3D CT scanning in end-inspiratory hold and end-expiration hold can be used to construct internal target volume instead of that based on 4D CT scanning in extreme phase for peripheral lung cancers, but spatital mismatches of GTVs are obvious between extreme phases in 4D CT and corresponding phases in 3D CT assisted with ABC, especially for tumors of smaller volume and with larger motion amplitude.

Purpose The purpose of this study was to explore the correlation between the respiration-induced target motion and volume variation with the dosimetric variance on breast and organ at risk (OAR) during free breathing. Methods and materials After breast-conserving surgery, seventeen patients underwent respiration-synchronized 4DCT simulation scans during free breathing. Treatment planning was constructed using the end inspiration scan, then copied and applied to the other phases and the dose distribution was calculated separately to evaluate the dose-volume histograms (DVH) parameters for the planning target volume (PTV), ipsilateral lung and heart. Results During free breathing, the treated breast motion vector was 2.09 ± 0.74 mm, and the volume variation was 3.05 ± 0.94%. There was no correlation between the breast volume and target/OAR dosimetric variation (|r| = 0.39 ~ 0.48). In the anteroposterior, superoinferior and vector directions, breast movement correlated well with the mean PTV dose, conformal index, and the lung volume receiving high dose (|r| = 0.651-0.975); in the superoinferior and vector directions, breast displacement only correlated with the heart volume receiving >5 Gy (V5) (r = −0.795, 0.687). The lung volume and the lung volume receiving high dose correlated reasonably well (r = 0.655 ~ 0.882), and a correlation only existed between heart volume and V5 (r = −0.701). Conclusion Target movement correlated well with the target/OAR dosimetric variation in certain directions, indicating that whole breast IMRT assisted by breathing control or respiratory-adapted gated treatment promotes the accuracy of dose delivery during radiotherapy. During free breathing, the effect of breast volume variation can be ignored in whole breast IMRT.

Enterovirus 71 (EV71) outbreaks are a socioeconomic burden, especially in the western Pacific region. Results of phase 1 clinical trials suggest an EV71 vaccine has a clinically acceptable safety profile and immunogenicity. We aimed to assess the best possible dose and formulation, immunogenicity, and safety profile of this EV71 vaccine in healthy Chinese children.This randomised, double-blind, placebo-controlled, phase 2 trial was undertaken at one site in Donghai County, Jiangsu Province, China. Eligible participants were healthy boys or girls aged 6–36 months. Participants were randomly assigned (1:1:1:1:1) to receive either 160 U, 320 U, or 640 U alum-adjuvant EV71 vaccine, 640 U adjuvant-free EV71 vaccine, or a placebo (containing alum adjuvant only), according to a blocked randomisation list generated by SAS 9.1. Participants and investigators were masked to the assignment. The primary endpoint was anti-EV71 neutralising antibody geometric mean titres (GMTs) at day 56, analysed according to protocol. The study is registered with ClinicalTrials.gov, number NCT01399853.We randomly assigned 1200 participants, 240 (120 aged 6–11 months [infants] and 120 aged 12–36 months [children]) of whom were assigned to each dose. 1106 participants completed the study and were included in the according-to-protocol analysis. The main reasons for dropout were withdrawal of consent and refusal to donate a blood sample. Infants who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (742·2 [95% CI 577·3–954·3]), followed by those who received the 320 U formulation (497·9 [383·1–647·0]). For children, those who received the 320 U formulation had the highest GMTs on day 56 (1383·2 [1037·3–1844·5]). Participants who received the vaccine had significantly higher GMTs than did who received placebo (p0·0001). For the subgroup of participants who were seronegative at baseline, both infants and children who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (522·8 [403·9–676·6] in infants and 708·4 [524·1–957·6] in children), followed by those who received the 320 U adjuvant vaccine (358·2 [280·5–457·5] in infants and 498·0 [383·4–646·9] in children). 549 (45·8%) of 1200 participants (95 CI 42·9–48·6%) reported at least one injection-site or systemic adverse reaction, but the incidence of adverse reactions did not differ significantly between groups (p=0·36). The 640 U alum-adjuvant vaccine group had a significantly higher incidence of induration than did the 640 U adjuvant-free group (p=0·001).Taking immunogenicity, safety, and production capacity into account, the 320 U alum-adjuvant formulation of the EV71 vaccine is probably the best possible formulation for phase 3 trials.The National Science and Technology Major Project (2011ZX10004-902) of the Chinese Ministry of Science and Technology, China's 12–5 National Major Infectious Disease Program (2012ZX10002-001), and Beijing Vigoo Biological.

To study the serum level of carbohydrate antigen 125 (CA125) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and the relation between serum CA125 and pulmonary hypertension. According to the results of pulmonary function and echocardiography, the subjects were

To measure the intrafraction displacement of the mediastinal metastatic lymph nodes of non-small cell lung cancer (NSCLC) based on four-dimensional computed tomography (4D-CT), and to provide the basis for the internal margin of metastatic mediastinal lymph nodes.Twenty-four NSCLC patients with mediastinal metastatic lymph nodes confirmed by contrast enhanced CT (short axis diameter ≥ 1 cm) were included in this study. 4D-CT simulation was carried out during free breathing and 10 image sets were acquired. The mediastinal metastatic lymph nodes and the dome of ipsilateral diaphragma were separately delineated on the CT images of 10 phases of breath cycle, and the lymph nodes were grouped as the upper, middle and lower mediastinal groups depending on the mediastinal station. Then the displacements of the lymph nodes in the left-right, anterior-posterior, superior-inferior directions and the 3-dimensional vector were measured. The differences of displacement in three directions for the same group of metastatic lymph nodes and in the same direction for different groups of metastatic lymph nodes were compared. The correlation between the displacement of ipsilateral diaphragma and mediastinal lymph nodes was analyzed in superior-inferior direction.The displacements in left-right, anterior-posterior and superior-inferior directions were (2.24 ± 1.55) mm, (1.87 ± 0.92) mm and (3.28 ± 2.59) mm for the total (53) mediastinal lymph nodes, respectively. The vectors were (4.70 ± 2.66) mm, (3.87 ± 2.45) mm, (4.97 ± 2.75) mm and (5.23 ± 2.67) mm for the total, upper, middle and lower mediastinal lymph nodes, respectively. For the upper mediastinal lymph nodes, the displacements in left-right, anterior-posterior and superior-inferior directions showed no significant difference between each other (P0.05). For the middle mediastinal lymph nodes, the displacements merely in anterior-posterior and superior-inferior directions showed significant difference (P = 0.005), while the displacements were not significantly different in the left-right and anterior-posterior, left-right and superior-inferior directions (P0.05). The displacements of the total and the lower mediastinal lymph nodes in left-right and superior-inferior, or anterior-posterior and superior-inferior directions were significantly different (P0.05), but was not significantly different in left-right and anterior-posterior directions (P0.05). The displacements of different group of mediastinal lymph nodes in a single direction or vector showed no significant difference (P0.05). In the superior-inferior direction, the correlation between the displacements of ipsilateral diaphragma and mediastinal lymph nodes were not statistically significant (P0.05).During free breathing, the differences between the intrafractional displacement of mediastinal metastatic lymph nodes in the same direction and its station were not statistically significant. The displacements of the total mediastinal metastatic lymph nodes in the superior-inferior direction were greater than that in the left-right and anterior-posterior directions, especially for the middle and lower mediastinal metastatic lymph nodes. There was no significant correlation between the displacements of ipsilateral diaphragma and the mediastinal metastatic lymph nodes in the superior-inferior direction, so it was unreasonable to estimate and predict the displacement of mediastinal metastatic lymph nodes by the displacement of ipsilateral diaphragma.

To compare the position and magnitude of internal target gross volume (IGTV) of primary hepatocarcinoma delineated by three methods based on four-dimensional computed tomography (4D-CT) and to investigate the relevant factors affecting the position and magnitude.Twenty patients with primary hepatocarcinoma after transcatheter arterial chemoembolization (TACE) underwent big bore 4D-CT simulation scan of the thorax and abdomen using a real-time position management (RPM) system for simultaneous record of the respiratory signals. The CT images with respiratory signal data were reconstructed and sorted into 10 phase groups in a respiratory cycle, with 0% phase corresponding to end-inhale and 50% corresponding to end-exhale. The maximum intensity projection (MIP) image was generated. IGTVs of the tumor were delineated using the following three methods: (1) The gross tumor volume (GTV) on each of the ten respiratory phases of the 4D-CT image set was delineated and fused ten GTV to produce IGTV10; (2) The GTVs delineated separately based on 0% and 50% phase were fused to produce IGTV(IN+EX); (3) The visible tumor on the MIP image was delineated to produce IGTV(MIP). Twenty patients were divided into groups A and B based on the location of the target center,and were divided into groups C and D based on the tumor maximum diameter. The patients were divided into groups E and F based on the three-dimensional (3D) motion vector of the target center. The position of the target center, the volume of target, the degree of inclusion (DI) and the matching index (MI) were compared reciprocally between IGTV10, IGTV(IN+EX) and IGTV(MIP), and the influence of the tumor position and 3D motion vector on the related parameters were compared based on the grouping.The average differences between the position of the center of IGTVs on direction of X, Y and Z axes were less than 1.5 mm, and the difference was statistically not significant. The volume of IGTV10 was larger than that of IGTV(IN+EX), but the difference was not significant (t = 0.354, P = 0.725). The volume of IGTV10 was larger than that of IGTV(MIP) but the difference was not significant (t = -0.392, P = 0.697). The ratio of IGTV(IN+EX) to IGTV10 was 0.75 +/- 0.15 and the ratio of IGTV(MIP) to IGTV10 was 0.78 +/- 0.14. The DI of IGTV(IN+EX) in IGTV10 was (74.85 +/- 15.09)% and that of IGTV(MIP) in IGTV10 was (68.87 +/- 13.69)%. The MI between IGTV10 and IGTV(IN+EX), IGTV10 and IGTV(MIP) were 0.75 +/- 0.15 and 0.67 +/- 0.13, respectively. The median of ratio of IGTV(IN+EX)/ IGTV10 was 0.57 in group A versus 0.87 in group B, statistically with a significant difference between the groups A and B (Z = -3.300,P = 0.001). The median of ratio of IGTV(MIP)/IGTV10 was 0.51 in the group A and 0.72 in group B, with a significant difference between the groups A and B (Z = -3.413, P = 0.001). The median of ratio of IGTV(IN+EX)/IGTV10 was 0.79 in group C versus 0.74 in group D, with a difference not significant (Z = -0.920, P = 0.358). The median of ratio of IGTV(MIP)/IGTV10 was 0.85 in group C versus 0.80 in group D, with a non-significant difference (Z = -0.568, P = 0.570). The median of ratio of IGTV(IN+EX)/IGTV10 was 0.87 in group E versus 0.68 in group F, with a significant difference between the two groups (Z = -2.897, P = 0.004). The median of ratio of IGTV(MIP)/IGTV10 was 0.85 in the group E versus 0.81 in the group F, with a non-significant difference (Z = -0.568, P = 0.570).The center displacement of the IGTVs delineated separately by the three techniques based on 4D-CT images is not obvious. IGTV(IN+EX) and IGTV(MIP) can not replace IGTV10, however, IGTV(IN+EX) is more close to IGTV10 comparing with IGTV(MIP). The ratio of IGTV10 and IGTV(MIP) is correlated to the 3D motion vector of the tumor. When the tumor is situated in the upper part of the liver and with a 3D motion vector less than 9 mm, IGTV10 should be the best IGTV.

To explore the displacement of the selected clips and the center of the geometry consisted of all the clips in the surgical cavity measured on the basis of four-dimensional computed tomography (4D-CT) simulation images.Fourteen breast cancer patients after breast-conserving surgery were recruited for external beam partial-breast irradiation (EB-PBI), and received large aperture CT simulation. The 4D-CT image data sets were collected when the patient was in the free breathing state. Using the Varian Eclipse treatment planning system, the selected four clips in the cavity were separately delineated on the CT images from 10 phases of the breath cycle, and all of the clips in the cavity were marked to obtain the geometry. Then the displacement of the four selected clips and the center of the geometry in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were measured. The differences of the displacement were compared.The displacements in the AP and SI directions were always greater than the displacement in LR direction for the same selected clip. The difference of the displacements in the same direction of the different selected clips was not statistically significant (P0.05). The displacements of the geometry center consisted of all of the clips in the LR, AP, SI directions were (1.34±0.39) mm, (2.01±1.02) mm and (1.89±1.03) mm, respectively, and the difference of the displacements between LR and AP, LR and SI were all statistically significant (P0.05). In the same directions (LR, AP and SI), the displacement of geometry center was always greater than the displacement of the selected clips, and the difference except SI direction was all statistically significant (P0.05). In the SI direction, the association between the displacement of geometry center and the upper clip, geometry center and the lower clip was statistically significant (P0.05).When the target for EB-PBI is defined on the basis of 4D-CT simulation images, the displacement of the selected clips at the border of the surgical cavity is not qualified to substitute the displacement of the target defined basing on all of the clips in the surgical cavity.

Background Enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD). Three inactivated EV71 whole-virus vaccines of different strains developed by different manufacturers in mainland China have recently entered clinical trials. Although several studies on these vaccines have been published, a study directly comparing the immunogenicity and protective effects among them has not been carried out, which makes evaluating their relative effectiveness difficult. Thus, properly comparing newly developed vaccines has become a priority, especially in China. Methods and Findings This comparative immunogenicity study was carried out on vaccine strains (both live and inactivated), final container products (FCPs) without adjuvant, and corresponding FCPs containing adjuvant (FCP-As) produced by three manufacturers. These vaccines were evaluated by neutralizing antibody (NAb) responses induced by the same or different dosages at one or multiple time points post-immunization. The protective efficacy of the three vaccines was also determined in one-day-old ICR mice born to immunized female mice. Survival rates were observed in these suckling mice after challenge with 20 LD50 of EV71/048M3C2. Three FCP-As, in a dose of 200 U, generated nearly 100% NAb positivity rates and similar geometric mean titers (GMTs), especially at 14–21 days post-inoculation. However, the dynamic NAb responses were different among three vaccine strains or three FCPs. The FCP-As at the lowest dose used in clinical trials (162 U) showed good protective effects in suckling mice against lethal challenge (90–100% survival), while the ED50 of NAb responses and protective effects varied among three FCP-As. Conclusions These studies establish a standard method for measuring the immunogenicity of EV71 vaccines in mice. The data generated from our mouse model study indicated a clear dose-response relationship, which is important for vaccine quality control and assessment, especially for predicting protective efficacy in humans when combined with future clinical trial results.

The aim of this study was to demonstrate the immunogenicity and safety of diphtheria, tetanus, pertussis (acellular, component), poliomyelitis (inactivated) vaccine (adsorbed) and Haemophilus influenzae type b conjugate vaccine (DTaP-IPV//PRP-T) combined vaccine compared with commercially available DTaP (diphtheria, tetanus and pertussis), Haemophilus influenzae type b (Hib), tetanus conjugate and IPV monovalent vaccine.Subjects were randomly divided into three groups, Group A and Group B were DTaP-IPV//PRP-T combined vaccine (PENTAXIM(TM)) vaccinated at 2, 3, 4 months of age or 3, 4, 5 months of age respectively; Group C was commercially available DTaP. Hib tetanus conjugate (Act-HIB(TM)) and IPV (IMOVAX PolioTM(TM)) vaccines vaccinated at 3, 4, 5 months of age. All groups received booster dose at 18 to 20 months of age, with antibody titers tested. Non-inferiority analysis was demonstrated in terms of seroprotection/seroconversion rates between Group A, Group B respectively and Group C. Safety information was collected after each vaccination to assess the safety of investigational vaccines.The non-inferiority of DTaP-IPV//PRP-T combined vaccine vaccinated at 2, 3, 4 or 3, 4, 5 months of age versus DTaP, Hib tetanus conjugate and IPV vaccine was demonstrated for all vaccine antigens in both primary and booster phases in terms of seroprotection/seroconversion rates. DTaP-IPV//PRP-T combined vaccine was well tolerated. The rate of solicited/unsolicited severe adverse reactions was very low and similar to the control vaccines.DTaP-IPV//PRP-T combined vaccine was highly immunogenic with good safety profile in Chinese infants, which was comparable to the commercially available control vaccines.

This study assessed the antibody persistence, and the immunogenicity and safety of a booster dose of a DTaP–IPV//PRP∼T (Pentaxim ® , Sanofi Pasteur's AcXim family) combined vaccine and of standalone vaccines one year after primary vaccination in the People's Republic of China. Participants ( N = 719) previously primed with DTaP–IPV//PRP∼T at 2, 3, 4 months (Group A, N = 255), 3, 4, 5 months (Group B, N = 233), or DTaP (Wuhan Institute of Biological Products), PRP-T (Act-Hib ® ) and IPV (Imovax ® Polio) at 3, 4, 5 months (Group C, N = 231) received boosters of the same vaccines at 18–20 months of age. Seroprotection (SP) and seroconversion (SC) were determined before and 1 month after the booster. Safety was monitored from parental reports. In all groups 87.6–100% of participants had pre-booster protective anti-PRP, -diphtheria, -tetanus and -poliovirus antibody titers; post-booster, all SP rates were 100% and SC was ≥80.4% for anti-pertussis titers ≥ 4-fold increase. Reactogenicity was low for each group. These data support the use of the DTaP–IPV//PRP∼T vaccine in the People's Republic of China compared to separate DTaP, IPV, and PRP∼T administration in terms of both safety and immunogenicity.

Enterovirus 71 (EV71) is one of the major causative agents of hand, foot and mouth disease. Recently, several EV71 inactivated vaccine candidates have been development in mainland China. To compare the antigenicity and genetic characteristics of different candidate vaccine strains for EV71, the genomes of 11 EV71 strains were sequenced. The cross-protection capacities were determined by neutralizing antibody test and were further assessed in neonatal mice. The results showed 93.0%–99.8% genome homology of the VP1 regions, but their cross-neutralization capacities varied. These results showed that vaccine strains with good cross-neutralization capacities had the potential to be vaccine strains.

Enterovirus 71 (EV71) and coxsackievirus A16 (Cox A16) are major causative agents for hand, foot and mouth disease (HFMD). Studies indicate that the frequent HFMD outbreaks result in a few hundreds children's death in China in recent years. The vaccine and other research for HFMD need to be developed urgently.to explore dynamic development of mother-source neutralizing antibodies against EV71 and Cox A16 in infants from Jiangsu Province, China, and to provide the fundamental data for further establishing of corresponding immunization course.Peripheral blood samples were collected from 133 of parturient women once immediately before delivery and their infants at two and seven months of age. Method of micro-dose cytopathogenic effect was used to measure neutralizing antibodies against EV71 and Cox A16, respectively.Seropositive rates of anti-EV71 and anti-Cox A16 in prenatal women were 79.7% (106/133) and 92.5% (123/133), respectively; geometric mean titers (GMTs) were 29.0 and 61.9; 75.9% (101/133) prenatal women were both positive in anti-EV71 and anti-Cox A16; seropositive rates of anti-EV71 and anti-Cox A16 were 25.6% (34/133) and 38.3% (51/133) in infants at two months of age; GMTs were 12.3 and 18.0, respectively. GMTs of anti-EV71 were significantly higher for infants at seven months (82.6) compared with that at two months (P0.05), showing infants had inapparently infected by EV71 during two to seven months. Although only one offspring (0.75%) at seven months was found having anti-Cox A16 transfered from maternal, this observation suggested no maternal antibody may remain in infants at seven months.The prevalence of EV71 and Cox A16 were relatively high in Jiangsu Province. Bivalent vaccine against both EV71 and Cox A16 should be developed, and the ideal time point for prime immunization for infants is around 2-5 months of age.

Two types of microbial fuel cells (MFCs) were adopted to analyze the effects of exoelectrogens and electron acceptors on the electrogenesis performance of MFCs. One was conventional MFCs inoculated with sewage and using nitrate as electron acceptor (S-MFCs), and the other one was modified MFCs inoculated with anaerobic treated wastewater and using ferricyanide as electron acceptor (A-MFCs). Exoelectrogens and electron acceptors had substantial effects on the acclimation period and the power output period of MFCs. The acclimation period was reduced from 500 h for S-MFCs to 430 h for A-MFCs, and the power output period was prolonged from 100 h for S-MFCs to 350 h for A-MFCs. The modified MFCs increased the removal of COD and the output of voltage by 25% and 300%, respectively. To select appropriate exoelectrogens and electron acceptors were crucial to the improvement of MFCs performance.

To evaluate the safety and immunogenicity of the booster dose of 7 valent pneumococcal conjugate vaccine (PCV7) to the healthy Chinese toddlers who had received 3 primary doses.Four hundred and eighty-eight Chinese toddlers received a booster dose of PCV7 at age of 12-15 months following a primary series of the vaccine given at ages 3, 4, 5 months separately with Diphtheria Tetanus Acellular Pertussis Combined Vaccine (DTaP) in Group 1 or concurrently with DTaP in Group 2. Following the booster dose immunization, each subject was followed up for 30 days to observe the safety of the vaccine. Blood samples were taken from a subset of subjects prior and post 30 days the booster dose immunization to evaluate immunogenicity.A high proportion of subjects in Group 1 (89%) and Group 2 (91%) remained afebrile after the booster dose. Local reactions to the PCV7 booster dose were generally mild. For each serotype, the rise in GMC (post-/pre-vaccination) showed a statistically significant difference (P0.0001) between both groups.PCV7 administered as a booster dose is generally safe, well tolerate, and immunogenic in healthy Chinese toddlers.

To investigate the characterization of the complete genome of EV71 in Beijing, 2008 and to provide basis for selecting appropriate virus strain to develop vaccine.12 throat swab samples were collected from children with hand-foot-mouth disease (HFMD). One sample named 08YM-3 was cultured and isolated in vero cells. Viral RNA was extracted and carried out by RT-PCR and 5', 3' rapid amplification of cDNA ends (RACE) to obtain the sequence from 08YM-3. PCR products were cloned and analyzed. Nucleotide identity between sequences was calculated and sequence alignments were made to generate phylogenetic trees using MegAlign in DNAStar.3 clones were constructed that covered EV71 complete genome. Data from sequences analysis showed that this viral strain named BJ08 shared 95.6%-96.7%, 88.3%-96.1%, 78.1%-94.0%, 90.8%-94.6%, 85.9%-94.1% and 90.9%-93.9% in 5' UTR, P1, P2, P3, 3' UTR region and complete genome with C4 subtype, respectively. BJ08 showed low nucleotides identity (90%) with other subtypes. Phylogenetic trees established from alignment of the complete genome and VP1 region indicated that BJ08 belonged to C4 subtype. BJ08 and C4 subtype strains shared the same amino acids in 6 sites in VP1 region, which were associated with EV71 subtype. There was no mutation in VP1 antigen epitope (92-107aa).This BJ08 strain belonged to C4 subtype. Further study on EV71 complete genome would have great significance for vaccine research.

In order to evaluate the safety and immunogenicity of group A + C meningococcal polysaccharide vaccine, a controlled field trial was performed among children at 6-24 months and 5-13 years old in Longsheng county, Guangxi Zhuang Autonomous Region.More than 600 children were selected in this trial. 428 children, aged 6-24 month-old and 5-13 year-old were involved in two experimental groups and were inoculated 100 microg of group A + C meningococcal polysaccharide vaccine. 103 children in positive control group were inoculated 50 microg of group A meningococcal polysaccharide vaccine while 94 children in negative control group were inoculated 30 microg of Typhoid Vi polysaccharide vaccine. Both systemic and local reactions were observed in each group at 6 h,24 h,48 h and 72 h after inoculation. Blood samples were collected in all children before and at 1 month after inoculation. Additionally, at least 50 blood samples were taken in each experimental group at 6 and 12 months after inoculation. Serum bactericidal antibody was tested by micro bactericidal test.Both systemic and local reactions were mild in two experimental groups with only 3 children (0.7%) hador = 37. 6 degrees C fever, 4 children (0.9%) appeared mild areola but all adverse reaction disappeared within 48 hours. In 5-13 year-old experimental group, the rates for four-fold increase of bactericidal antibody were 96.59% and 92.15% to group A and group C meningococcus respectively at 1 month after inoculation, and remained 90.91% and 90.08% at 12 months after inoculation.Group A + C meningococal polysaccharide vaccine was safe and having good immunogenicity among Chinese children.

Objective: To measure the intra-fraction displacements of the mediastinal metastatic lymph nodes by using four-dimensional CT (4D-CT) in non-small cell lung cancer (NSCLC). Materials and Methods: Twenty-four patients with NSCLC, who were to be treated by using three dimensional conformal radiation therapy (3D-CRT), underwent a 4D-CT simulation during free breathing. The mediastinal metastatic lymph nodes were delineated on the CT images of 10 phases of the breath cycle. The lymph nodes were grouped as the upper, middle and lower mediastinal groups depending on the mediastinal regions. The displacements of the center of the lymph node in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were measured. Results: The mean displacements of the center of the mediastinal lymph node in the LR, AP, and SI directions were 2.24 mm, 1.87 mm, and 3.28 mm, respectively. There were statistically significant differences between the displacements in the SI and LR, and the SI and AP directions (p < 0.05). For the middle and lower mediastinal lymph nodes, the displacement difference between the AP and SI was statistically significant (p = 0.005; p = 0.015), while there was no significant difference between the LR and AP directions (p < 0.05). Conclusion: The metastatic mediastinal lymph node movements are different in the LR, AP, and SI directions in patients with NSCLC, particularly for the middle and lower mediastinal lymph nodes. The spatial non-uniform margins should be considered for the metastatic mediastinal lymph nodes in involved-field radiotherapy. Index terms: Non-small cell lung cancer; Four-dimensional computed tomography; Mediastinal lymph nodes; Displacement measurement

Enterovirus 71 (EV71) is a highly infectious agent that causes hand–foot–mouth disease (HFMD) in humans. Effective vaccination against EV71 infection is critically important, given the recent outbreak of HFMD in the Asia-Pacific region, where it has shown significant mortality and morbidity. There is currently no approved anti-viral therapy available to treat the disease. While several vaccine manufacturers are actively developing EV71 vaccines, there are no international reference standards available to conduct quality control on EV71 vaccines or to assess the effectiveness of EV71 vaccines in immunized populations. In the current report, antigen reference standard based on the C4 subtype of the EV71 vaccine strain was developed. In addition, neutralizing antibody (NTAb) reference panels were analyzed and standards with various neutralizing titers were selected. These reference antigens were used to calibrate vaccine samples from several producers and found that five EV71 antigens and the national reference standards showed good linearity and parallelism. Moreover, mice immunized with various vaccines at doses standardized by these national references showed comparable NTAb responses. Finally, the national NTAb reference panels were found to effectively reduce assay discrepancy between different labs. Taken together, these national reference standards are highly valuable for the standardization and evaluation of EV71 vaccines.