LncRNA H19 Inhibits the Progression of Sepsis-Induced Myocardial Injury via Regulation of the miR-93-5p/SORBS2 Axis.

Sepsis is an infectious disease that seriously endangers human health. It usually leads to myocardial injury which seriously endangers to the health of human beings. H19 has been confirmed to play key roles in various diseases, including sepsis. However, its function in the progression of sepsis-induced myocardial injury remains largely unknown. H9C2 cells were treated with lipopolysaccharide (LPS) to mimic sepsis-induced myocardial injury in vitro. Cell proliferation and apoptosis were detected by MTT assay and flow cytometry, respectively. In addition, gene and protein expression levels in H9C2 cells were measured by quantitative real-time PCR (qRT-PCR) and Western blotting. The levels of inflammatory cytokines in H9C2 cell supernatants were tested by ELISA. JC-1 staining was performed to observe the mitochondrial membrane potential level in H9C2 cells. H19 and SORBS2 were downregulated in H9C2 cells following LPS treatment, while miR-93-5p was upregulated. Moreover, LPS-induced cell growth inhibition and mitochondrial damage were significantly reversed by overexpression of H19. In addition, H19 upregulation notably suppressed LPS-induced inflammatory responses in H9C2 cells. Moreover, H19 sponged miR-93-5p to promote SORBS2 expression. Overall, H19 suppressed sepsis-induced myocardial injury via regulation of the miR-93-5p/SORBS2 axis. H19 attenuated the development of sepsis-induced myocardial injury in vitro via modulation of the miR-93-5p/SORBS2 axis. Thus, H19 could serve as a potential target for the treatment of sepsis-induced myocardial injury.

Locating lost radioactive sources using a UAV radiation monitoring system.

Locating lost radioactive sources quickly, precisely, and safely is very important in emergency responses of lost radioactive source accidents. This paper describes a source localization approach using an independently developed unmanned aerial vehicle (UAV) radiation monitoring system, which uses a specialized source localization algorithm. Once a radiation anomaly spot is found on the ground, an L×L (m2) square area around the anomaly spot defined as suspicious region is selected to perform an accurate source localization. Then, the UAV radiation monitoring instrument is dispatched to hover at some scheduled detection positions within the suspicious region for radiation measurements. After the last hover finished, the actual source position is calculated by the source localization algorithm program in real time. The source localization algorithm was developed on the basis of the inverse-square law and statistical methods. Five critical factors of the algorithm that may lead to errors in localization such as the meshing number in calculations, the size of the suspicious region, the number of the detection positions, the distribution of the detection positions, and the coverage range of the detection positions were studied by using measurement data from Monte Carlo simulations. Subsequently, the approach was experimentally verified for a 3.7 × 107 Bq 131I source localization. Three experimental scenes were applied such as the source on the grass, next to a tree, and in a puddle. Different distributions of the detection positions and different numbers of the detection positions were studied. The best localization distance error was 30 cm within a 10 × 10 m2 suspicious region, and the calculation time was not more than 0.1 s after a total survey flight of 5 min.

Analysis on the emission and potential application of Cherenkov radiation in boron neutron capture therapy: A Monte Carlo simulation study.

This paper was aimed to explore the physics of Cherenkov radiation and its potential application in boron neutron capture therapy (BNCT). The Monte Carlo toolkit Geant4 was used to simulate the interaction between the epithermal neutron beam and the phantom containing boron-10. Results showed that Cherenkov photons can only be generated from secondary charged particles of gamma rays in BNCT, in which the 2.223 MeV prompt gamma rays are the main contributor. The number of Cherenkov photons per unit mass generated in the measurement region decreases linearly with the increase of boron concentration in both water and tissue phantom. The work presented the fundamental basis for applications of Cherenkov radiation in BNCT.

Optimization of the Compton camera for measuring prompt gamma rays in boron neutron capture therapy.

Optimization of the Compton camera for measuring prompt gamma rays (0.478MeV) emitted during boron neutron capture therapy (BNCT) was performed with Geant4. The parameters of the Compton camera were determined as follows: 3cm thick - 10cm wide scatter detector (Silicon), 10cm thick - 10cm wide absorber detector (Germanium), and 1cm distance between the scatter and absorber detectors. For a typical brain tumor treatment, the overall detection efficiency of the optimized Compton camera was approximately 0.1425% using the Snyder's head phantom with a sphere tumor (4cm diameter and ~1cm depth).

Comparison between Dual Arc VMAT and 7F-IMRT in the protection of hippocampus for patients during whole brain radiotherapy.

PURPOSE: The purpose of this study was to compare the dosimetric characteristics for protection of the hippocampus between dual arc VMAT (volumetric modulated arc therapy) and 7 fields intensity-modulated radiation therapy (7F-IMRT) for patients with brain metastases from lung cancer under the whole brain radiotherapy. METHODS: Based on ten cases with brain metastases from lung cancer, two types of radiotherapy plans were designed, namely, dual arc VMAT and 7F-IMRT. Provided that the clinical requirements were satisfied, the comparisons of target dose distribution, conformity index (CI), homogeneity index (HI), dose of organs at risk (OARs), monitor units (MU) and treatment time between dual arc VMAT and 7F-IMRT were investigated for their dosimetric difference. RESULTS: Both treatment plans met the requirements of clinical treatments. However, the PTV-HA conformity and homogeneity of dual arc VMAT were superior to those of 7F-IMRT (P < 0.05). As to OARs, the mean maximum doses (Dmax) of hippocampus, eyes and optic nerves in the dual arc VMAT plan were all lower than those in 7F-IMRT plan (P < 0.05), but the result had no statistical significance (P < 0.05) for the maximum dose of lens. Compared with 7F-IMRT, dual arc VMAT reduced the average number of MU by 67% and the average treatment time by 74%. Therefore, treatment time was shortened by dual arc VMAT. CONCLUSION: With regards to the patients with brain metastases from lung cancer under the whole brain radiotherapy, the PTV-HA conformity and homogeneity of dual arc VMAT were superior to those of 7F-IMRT under the precise of meeting the clinical requirements. In addition, dual arc VMAT remarkably reduced the irradiation dose to OARs (hippocampus, eyes and optic nerves), MU and treatment time, as well, guaranteed patients with better protection.

Analysis of the setup errors of medical image registration-based cone-beam CT for lung cancer.

PURPOSE: This study aimed to investigate the feasibility of efficiently using a rigid image registration (RIR) algorithm or a deformable image registration (DIR) algorithm to match medical images and evaluate the impact of setup errors on intensity modulated radiation therapy of lung cancer patients. METHODS: Ten lung cancer patients were chosen randomly each day and were subjected to image-guided radiotherapy. The clinical registration between cone-beam computed tomography (CBCT) images and treatment planning system CT images was performed by applying both RIR and DIR; the clinical registration was evaluated on the basis of the contour index, including dice similarity coefficient, sensitivity, and positive predictive value; the optimal scheme of image registration was selected to ensure that the actual irradiation isocenter was consistent with the treatment planning isocenter. In each patient, the translational errors in the right-left (x), superior-inferior (y), and anterior-posterior (z) directions and the rotational errors in the u, υ, and w directions formed by the x, y, and z directions were calculated and analyzed daily in the whole course of treatment; margins were calculated according to this equation: M = 2.5∑+ 0.7δ. RESULTS: The tumors and the surrounding soft tissues of the patients are shown more clearly in the CBCT images than in the CT images. DIR can be applied more efficiently than RIR to determine the morphological and positional changes in the organs shown in the images with the same or different modalities in the different period. The setup errors in translation in the x, y and z axes were 0.05±0.16, 0.09±0.32 and -0.02±0.13 cm, respectively; by contrast, the setup errors in rotation in u, υ and w directions were (0.41±0.64)°, (-0.08±0.57)° and (-0.03±0.62)°, respectively. The setup errors in the x, y and z axes of the patients indicated that the margins expansions were 0.82, 1.15 and 0.72 cm, respectively. CONCLUSION: CBCT with DIR can measure and correct the setup errors online; as a result, setup errors in lung cancer treatments can be significantly reduced and the accuracy of radiotherapy can be enhanced.

Efficiency calibration and minimum detectable activity concentration of a real-time UAV airborne sensor system with two gamma spectrometers.

A small-sized UAV (NH-UAV) airborne system with two gamma spectrometers (LaBr3 detector and HPGe detector) was developed to monitor activity concentration in serious nuclear accidents, such as the Fukushima nuclear accident. The efficiency calibration and determination of minimum detectable activity concentration (MDAC) of the specific system were studied by MC simulations at different flight altitudes, different horizontal distances from the detection position to the source term center and different source term sizes. Both air and ground radiation were considered in the models. The results obtained may provide instructive suggestions for in-situ radioactivity measurements of NH-UAV.

Temperature effect of a radioluminescent nuclear battery based on (147)Pm/ZnS:Cu/GaAs.

A radioluminescent nuclear battery was fabricated and the performance was measured and calculated at temperature of 223.15-323.15K. Experimental and theoretical results indicate that Jsc minimally decreases with the increase in temperature, whereas Voc linearly decreases. Pmax rapidly decreases with temperature. The mechanism of temperature effect is discussed using the temperature dependency of semiconductor parameters. This study significantly guides the selection of batteries' power source under various temperature. The nuclear battery may also be used as a long-life temperature transducer.

[Comparison of open and endovascular repair for abdominal aortic aneurysm mid-term outcomes: a single center randomized controlled trial].

OBJECTIVE: To compare the effects of open and endovascular repair for abdominal aortic aneurysm. METHODS: Between January 2009 and January 2011, 84 patients were randomized to endovascular aneurysm repair (EVAR) or open repair. There were 48 patients in EVAR group, 42 cases were male (87.5%), 6 cases were female (12.5%), aged from 50 to 83 years with a mean of 70.8 years. There were 36 patients in open repair group, 31 cases were male (86.1%), 5 cases were female (13.9%), aged from 50 to 80 years with a meal of 67.4 years. The results of perioperative period and follow-up were analyzed. RESULTS: Between the two groups, there was significant difference on operative time (t = 9.863, P = 0.000), blood loss (t = 4.647, P = 0.000), blood transfusion (t = 3.334, P = 0.002), hospital stay (t = 2.327, P = 0.022), and medical expense (t = 2.314, P = 0.023). There was no significant difference for perioperative complications (χ(2) = 0.480, P = 0.488). There was no significant difference for complications (χ(2) = 0.664, P = 0.415) and mortality (P = 0.429) during 3 months follow-up. There was no significant difference for complications during 6 months follow-up (χ(2) = 0.128, P = 0.720). CONCLUSIONS: Operative time, blood loss and transfusion, hospital stay in EVAR group are less than which in open repair group, the medical expense of EVAR was higher than open repair. There is no significant difference for complications during 6 months follow-up between 2 groups. Long-term follow-up and more patents are needed to analyze survival rate and long-term complications.

[Preliminary study on differential expression of plasma proteins of patients with Takayasu's arteritis in different stage].

OBJECTIVES: To investigate differential expression of plasma proteins of patients with Takayasu's arteritis to screen disease-related or phase-related proteins or biomarkers. METHODS: From March, 2005 to January, 2006, Plasma of 20 patients with acute Takayasu's arteritis, 20 patients with chronic Takayasu's arteritis, and 20 healthy people as control were collected. Plasma proteins were profiled by two-dimensional electrophoresis. Spots of differential expression were screened by computerized map analysis and identified by matrix assisted laser desorption/ionization time of flight-mass spectrometry. Circulation levels of parts of differential expression proteins were investigated by Elisa in each subject. RESULTS: Fourteen differential expression proteins were identified, including serum amyloid A, serum amyloid P, fibrinogen, complement C3c, C7, C4 binding protein, factor H related protein-1, immunoglobin, alpha-acid glycoprotein, RAG1 protein, alpha1-microglobin, apolipoprotein A-I, A-IV, transthyretin, haptoglobin. Proteins related to acute and chronic phase were serum amyloid A, fibrinogen, transthyretin, haptoglobin; Circulation levels of Serum amyloid A (SAA) and Complement C4 binding protein (C4BP) were significantly increased in active TA patients comparing to that in inactive TA patients and in controls (SAA: 95.9 vs 49.2, P = 0.009 and 23.9 mg/L, P = 0.001, respectively; C4BP: 88.5 vs 61.7, P = 0.023 and 32.6 mg/L, P < 0.001, respectively). CONCLUSIONS: Acute phase proteins and immune proteins may possible be markers for diagnosis and activity of Takayasu's arteritis, Complement activity, complement modulation protein and antibody production may be involved in immune mechanism of Takayasu's arteritis. Further study of these proteins may be helpful to elucidate the pathologic mechanism of Takayasu's arteritis.

[Comparison of open and endovascular repair for abdominal aortic aneurysm].

OBJECTIVE: To compare the effects of open and endovascular repair for abdominal aortic aneurysm. METHODS: From January 2002 to July 2007, clinical data of 223 patients with infrarenal abdominal aortic aneurysm undergoing open (141 patients) or endovascular repair (82 patients) were retrospectively reviewed. The intra- and post-operative complications, mortality, complications, survival, life quality, and cost during follow-up were analyzed. RESULTS: Operative time in endovascular group was significantly shorter than open repair group. Blood loss and transfusion in endovascular group were significantly less than open repair group (P < 0.01). There was no significant difference of intra- and post-operation complications (P > 0.05). Six-month total SF-36 scores were significantly higher in open repair group compared with endovascular group. There was no significant difference of survival rate at 2 years (P > 0.05), but endovascular group had fewer complications (P < 0.01). CONCLUSIONS: Endovascular repair is mini-invasive, but has more complications of long-term follow-up. The life quality in open repair group is better than endovascular group, and a prospective random trial is required.

Cluster specific regulation pattern of upstream regulatory elements in human alpha- and beta-globin gene clusters.

Located in different chromatin contexts and with different developmental switching mode, human alpha- and beta-globin gene clusters are co-regulated temporally and quantitatively to keep balanced expression. Here, by exchanging their key upstream regulatory elements (UREs) in cluster level, and investigating the expression level of exogenous globin genes in the bacterial artificial chromosome (BAC) mediated transgenic mice, we explored the similarities and differences in the regulatory effects between alpha-upstream regulatory element (alpha-URE) and beta-locus control region (beta-LCR). The results showed that, after exchange, the developmental switching modes of human alpha- and beta-like globin genes had changed, with lost expression of epsilon- and alpha1-genes. Their expression levels also decreased. Our study suggests that the regulation of alpha-URE and beta-LCR on the expression level and developmental switching mode of downstream globin genes is cluster specific.

[Change of the chromosome conformation of human alpha-globin gene locus in transgenic mice].

OBJECTIVE: To establish chromosome conformation capture (3C) strategy and to use this method for exploring the effect of chromosome conformation on human alpha-globin gene expression in the human alpha-globin transgenic mouse. METHODS: Homozygous human alpha-globin transgenic male mouse was crossed with KM female mouse. The 14.5-day post-coitum (dpc) embryos were used for the isolation of fetal liver and fetal brain cells. Homogeneous single-cell suspension was treated with formaldehyde to crosslink the chromatin conformation in the nuclear. The cross-linked chromatin compound was digested with Nco I and then ligated with T4 DNA ligase. The ligated compound was reversely cross-linked and then the ligated genomic DNA was purified for PCR analysis. The primers were designed along the two sides of cut and ligated sites. Semi-quantitative PCR was used to analyze the chromosome conformation of the whole human alpha-globin gene locus in fetal liver and fetal brain cells. RESULTS: When HS40 fragment was used as the fixed fragment, in fetal brain cells, the ligation frequencies of HS40 fragment with other fragments were decreased as the linear distances to HS40 fragment were increasing; while in fetal liver cells, two active genes (alpha1 and alpha2) fragments showed higher ligation frequencies with HS40 fragment than other fragments. However, the fragment containing an inactive gene (xi) displayed the comparable low ligation frequency as that in fetal brain. When alpha2 fragment was used as the fixed fragment, similarly, in fetal brain cells the ligation frequencies of alpha2 fragment with other ones were decreased as the linear distances increasing; when in fetal liver cells, it showed higher ligation frequencies with two upstream regulatory elements (HS 40 and 33). However, it showed a little bit lower ligation frequency with another two upstream regulatory elements (HS10 and 8) than those in fetal brain. CONCLUSION: In fetal liver cells, the distant regulatory elements are in close proximity to the downstream of the expressed globin genes through looping out, the interval region; however, in fetal brain, they were not in vicinity to the expressed globin genes.

[Problems and strategies for reoperation of vascular diseases].

Appropriate reoperation of the lower extremity artery may be required because of graft stenosis, occlusion, and infection. For high-risk patients who have no autogeneic vein available or who are not suitable for open reoperation, endoluminal plasty may be an alternative. The options of treatment for abdominal aortic aneurysm include traditional procedures and endovascular aneurysm repair (EVAR). The reintervention rate is higher in EVAR than in traditional procedures. The options of treatment for recurrent carotid artery stenosis remain controversial. The advantages and disadvantages of carotid endarterectomy (CEA) and carotid artery stent (CAS) should be compared under comparable clinical situations.

HS-48 alone has no enhancement role on the expression of human alpha-globin gene cluster.

To investigate the in vivo function of the newly defined DNase I hypersensitive site HS-48 on the whole human alpha-globin gene cluster, the region containing all the other known 5 hypersensitive sites HS-4 to HS-40 was deleted from a 117 kb bacterial artificial chromosome clone bearing the whole human alpha-globin gene cluster. Transgenic mice were generated from this construct. The RNase protection assays showed that with HS-48 left and all the other 5 hypersensitive sites deleted, the expression of human alpha-like globin genes was completely silenced in embryonic, fetal and adult stages in all tissues. This finding indicates that HS-48 alone has no enhancer activity on the expression of human alpha-like globin genes, and that the region of HS-4 to HS-40 already contains all the upstream cis-elements needed for regulating human alpha-like globin genes.

A conserved, extended chromatin opening within alpha-globin locus during development.

Histone modifications play an important role in eukaryotic gene regulation. However, the dynamic alteration of histone modification during development is poorly understood. In addition, the relationship between histone modification and globin gene switching remains unclear. Here, we assessed the dynamic pattern of histone modification (H3 acetylation, H4 acetylation, H3 K4 methylation, and H3 K79 methylation) along the murine alpha-globin locus, as well as along the human alpha-globin locus in transgenic mice, during globin gene switching in vivo. During the switching, histone modification at embryonic zeta-gene and fetal/adult alpha-genes displayed different developmental patterns. The level of histone modification at zeta-gene was developmentally regulated, in accordance with the level of zeta-gene expression, whereas the alpha-genes kept high level of histone modification at both developmental stages, regardless of their expression levels. Histone deacetylase inhibition selectively increased acetylation at the inactive zeta-gene in fetal livers, although it did not reactivate the gene expression. More importantly, an obvious increasing of histone modification level at major regulatory elements and fetal/adult alpha-genes was observed during the switching, suggesting that a conserved, extended chromatin opening within the locus occurs during globin gene switching.

No existence of translocus balancer to coordinate the expression and regulation of human hemoglobin genes in transgenic mice study.

All mammals use hemoglobin (Hb) to transport oxygen. Each Hb molecule is a tetramer of two pairs of unlike globin polypeptide chains. Equal amount of subunit globin chains derived from the corresponding alpha- and beta-like genes can always result during development though the two separate gene clusters are located on two different chromosomes and spatially transcribed within different nuclear domains. Disturbance of this balance will result in degradation or precipitation of the excessive globin chains, which is the character of various thalassemic syndromes. In previous studies, we had established two kinds of bacterial artificial chromosome (BAC) mediated transgenic mouse models, which contain respectively the entire human alpha- and beta-globin cluster. Here, we investigated the regulatory relationship between the two clusters by interbreeding these two kinds of transgenic mice. The levels of human alpha- and beta-mRNA in the various hybrid lines reflect the levels in the original transgenic lines that contain either the alpha- or beta-globin cluster alone. The results suggested that there is no apparent cross talk or regulatory interaction between the two human globin clusters in transgenic mice.