Efficacy and safety of flumatinib in the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase: A real-world single-center retrospective study, with a focus on premature drug discontinuation.

PURPOSE: To assess the real-world efficacy and safety of flumatinib as first-line and post-line treatments for chronic myeloid leukemia in the chronic phase (CML-CP). RESULTS: Among 141 patients receiving flumatinib as first-line and post-line treatment, the 12-month major molecular response (MMR) rates were 69.4% and 67.6%, respectively. The median time to response was 6 and 10.5 months, respectively. In post-line treatment, the early molecular response (EMR) of flumatinib as second-line is significantly superior to that of third-line treatment (3-month EMR rate: 79.2% vs. 39.3%, P<0.001; 3-month MMR rate: 45.8% vs. 21.4%, P=0.033). Contrastively, patients who switched to flumatinib due to intolerance had significantly higher MMR rates at 3, 6, and 12 months compared to patients who switched due to inadequate response (60.6% vs. 24.2%, P=0.003; 66.7% vs. 36.0%, P=0.027; 84.2% vs. 50.0%, P=0.038). Premature drug discontinuation was observed in 28.4% of the patients. Grades 3-4 hematologic adverse events (AEs) were identified as independent risk factors for premature drug discontinuation. Patients who discontinued treatment and those who previously received only imatinib therapy had a poorer molecular response and failure-free survival. CONCLUSIONS: Flumatinib demonstrates favorable efficacy and safety. Treatment discontinuation can result in a poorer molecular response and long-term prognosis.

Oxymatrine Modulation of TLR3 Signaling: A Dual-Action Mechanism for H9N2 Avian Influenza Virus Defense and Immune Regulation.

In our research, we explored a natural substance called Oxymatrine, found in a traditional Chinese medicinal plant, to fight against a common bird flu virus known as H9N2. This virus not only affects birds but can also pose a threat to human health. We focused on how this natural compound can help in stopping the virus from spreading in cells that line the lungs of birds and potentially humans. Our findings show that Oxymatrine can both directly block the virus and boost the body's immune response against it. This dual-action mechanism is particularly interesting because it indicates that Oxymatrine might be a useful tool in developing new ways to prevent and treat this type of bird flu. Understanding how Oxymatrine works against the H9N2 virus could lead to safer and more natural ways to combat viral infections in animals and humans, contributing to the health and well-being of society. The H9N2 Avian Influenza Virus (AIV) is a persistent health threat because of its rapid mutation rate and the limited efficacy of vaccines, underscoring the urgent need for innovative therapies. This study investigated the H9N2 AIV antiviral properties of Oxymatrine (OMT), a compound derived from traditional Chinese medicine, particularly focusing on its interaction with pulmonary microvascular endothelial cells (PMVECs). Employing an array of in vitro assays, including 50% tissue culture infectious dose, Cell Counting Kit-8, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot, we systematically elucidated the multifaceted effects of OMT. OMT dose-dependently inhibited critical antiviral proteins (PKR and Mx1) and modulated the expression of type I interferons and key cytokines (IFN-α, IFN-ß, IL-6, and TNF-α), thereby affecting TLR3 signaling and its downstream elements (NF-κB and IRF-3). OMT's antiviral efficacy extended beyond TLR3-mediated responses, suggesting its potential as a versatile antiviral agent. This study not only contributes to the growing body of research on the use of natural compounds as antiviral agents but also underscores the importance of further investigating the broader application of OMT for combating viral infections.

Cecropin AD reduces viral load and inflammatory response against H9N2 avian influenza virus in chickens.

Introduction: This study focuses on evaluating the therapeutic efficacy of cecropin AD, an antimicrobial peptide, against H9N2 avian influenza virus (AIV) in chickens. Given the global impact of H9N2 AIV on poultry health, identifying effective treatments is crucial. Methods: To assess the impact of cecropin AD, we conducted in vivo experiments involving 108 5-week-old chickens divided into control, infected, and various treatment groups based on cecropin AD dosage levels (high, medium, and low). The methodologies included hemagglutination (HA) tests for viral titers, histopathological examination and toluidine blue (TB) staining for lung pathology, real-time PCR for viral detection, and enzyme-linked immunosorbent assays for measuring serum levels of inflammatory markers. Results: The findings revealed that cecropin AD substantially reduced lung pathology and viral load, especially at higher dosages, comparing favorably with the effects seen from conventional treatments. Moreover, cecropin AD effectively modulated mast cell activity and the levels of inflammatory markers such as IL-6, TNF-α, IFN-γ, and 5-HT, indicating its potential to diminish inflammation and viral spread. Discussion: Cecropin AD presents a significant potential as an alternative treatment for H9N2 AIV in chickens, as evidenced by its ability to lessen lung damage, decrease viral presence, and adjust immune responses. This positions cecropin AD as a promising candidate for further exploration in the management of H9N2 AIV infections in poultry.

Isorhamnetin Regulates Programmed Death Ligand-1 Expression by Suppressing the EGFR-STAT3 Signaling Pathway in Canine Mammary Tumors.

Programmed death ligand-1 (PD-L1) is highly expressed in a variety of cancer cells and suggests a poorer prognosis for patients. The natural compound isorhamnetin (ISO) shows promise in treating cancers and causing damage to canine mammary tumor (CMT) cells. We investigated the mechanism of ISO in reducing PD-L1 expression in CMT cells. Clustered, regularly interspaced short palindromic repeat-associated protein 9 (CRISPR/Cas9) was used to mediate CD274 knockout in U27 cells. Then, monoclonal cells were screened and cultured. Nucleotide sequencing and expression of PD-L1 were detected. Additionally, we examined cell migration, invasion, and damage. Immunofluorescent staining of PD-L1 was examined in U27 cells. The signaling pathways were measured by Western blotting. Murine xenotransplantation models and murine immunocompetent allograft mammary tumor models were established to evaluate the effect of ISO therapy. Expression of Ki-67, caspase3, and PD-L1 were analyzed by immunohistochemistry. A pull-down assay was used to explore which proteins could bind to ISO. Canine EGFR protein was purified and used to detect whether it directly binds to ISO using a surface plasmon resonance assay. ISO inhibited the EGFR-STAT3-PD-L1 signaling pathway and blocked cancer growth, significantly increasing the survival rate of healthy cells. The cell membrane receptor EGFR was identified as a direct target of ISO. ISO could be exploited as an antineoplastic treatment of CMT by targeting EGFR to suppress PD-L1 expression.

Development of Low-Pressure He-MC-MIP-MS and Its Application for Oxygen Isotopic Analysis.

In Ar-based inductively coupled plasma mass spectrometry (MS), Ar-related interference and the low ionization capacity of the Ar-ion source prevent facile and precise determination of certain elements. To address this problem, we investigated the application of microwave-induced plasma (MIP), and we improved its ionization capacity using He as the working gas. The MIP ion source was connected to a multicollector mass spectrometry (MC-MS) apparatus to improve the accuracy and precision of the isotopic analysis. A vacuum pump was used to achieve a low pressure (200-300 Pa) at the interface. The analytical figures of merit were discussed and evaluated by measuring the oxygen isotopes in oxygen. With the application of low-pressure He-MC-MIP-MS, the degree of ionization of oxygen could be significantly improved with He plasma. The interference of oxygen from the atmosphere could also be eliminated with low-pressure plasma, and the determination precision of oxygen isotopes could be improved with the application of MC-MS. Subsequently, using this method, 16O18O/16O16O was applied as the analytical ratio to investigate the interference, sensitivity, and precision. With this constructed method, the obtained long-term producibility of δ18O was 0.16‰ (2 SD), and the measured result for oxygen was consistent with that obtained by MAT 253 within the uncertainty limit. The development of low-pressure He-MC-MIP-MS can pave the way for the accurate measurement of nonmetal isotopes and easily interfered isotopes in Ar plasma.

1,8-Cineole Alleviates OGD/R-Induced Oxidative Damage and Restores Mitochondrial Function by Promoting the Nrf2 Pathway.

This study examined the effects of 1,8-cineole on reducing oxidative stress injury and restoring mitochondrial function in oxygen-glucose deprivation and reoxygenation (OGD/R) HT22 cells via the nuclear factor erythrocyte 2 related factor 2 (Nrf2) pathway. The optimal concentration of 1,8-cineole to reduce OGD/R injury was screened via cell morphology, cell survival rate, and lactate dehydrogenase (LDH) leakage rate. Oxidative damage was observed by measuring superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) activities, and reactive oxygen species (ROS), glutathione (GSH), protein carbonyl, malondialdehyde (MDA), lipid peroxidation (LPO) content, and 8-hydroxy-2 deoxyguanosine (8-OHDG) expression. Mitochondrial function was observed by mitochondrial membrane potential (MMP) and ATPase activity. Nrf2 pathways were observed by the expression levels of total Nrf2, nucleus Nrf2, reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H): quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), the mRNA levels of HO-1 and NQO1. Among different concentrations of 1,8-cineole for promoting HT22 cell proliferation and attenuated OGD/R injury, 10 µmol/L 1,8-cineole was the best. After 1,8-cineole treatment, SOD, GSH-PX, and CAT activities and GSH content increased, while ROS, MDA, LPO, protein carbonyl, and 8-OHDG levels decreased. 1,8-Cineole could restore MMP and increase mitochondrial enzyme activity. It could also increase the total Nrf2, nucleus Nrf2, NQO1, and HO-1, and Nrf2 inhibitor brusatol reduced the effect of 1,8-cineole. Immunofluorescence assay showed that 1,8-cineole could facilitate the transfer of Nrf2 into the nucleus. 1,8-cineole increased the mRNA levels of NQO1 and HO-1. The above results showed that 1,8-cineole could alleviate OGD/R-induced oxidative damage and restores mitochondrial function by activating the Nrf2 signal pathway.

Experimental study on the leakage temperature field of buried CO2 pipelines.

The leakage of small holes in the buried CO2 pipeline is not easy to detect, which leads to the problem of the inability to accurately trace the source of the pipeline repair in the later stage. This paper designs and builds an experimental system to simulate the leakage of buried CO2 pipelines and conducts experiments on the leakage of small holes in buried CO2 pipelines to investigate the changes in the surrounding soil temperature when they leak. The results showed that the type of movement of CO2 in porous media after it is released from the leak is "funneling." At a distance of about 50 mm from the horizontal, the temperature difference in the horizontal surface is smallest at the 50 cm closest to the vertical distance of the leak, while at a distance of 225 mm from the horizontal, the temperature difference in the horizontal surface is largest at the 70 cm farthest from the vertical distance of the leak. The research results can provide a theoretical basis for the later development of technologies that can quickly locate the leakage points of buried CO2 pipelines and accurately determine their leakage status.

The Damage to Thick Steel Plates by Local Contact Explosions.

The paper presents the damage results of thick steel plates subjected to local blast loading using experimental and numerical approaches. Three steel plates with a thickness of 17 mm under the local contact explosion of trinitrotoluene (TNT) explosives were tested, and the damaged parts of the steel plates were scanned using a scanning electron microscope (SEM). ANSYS LS-DYNA software was used to simulate the damage results of the steel plate. By analyzing and comparing the experimental results with the numerical simulation results, the influence law of the TNT acting on the steel plate, the damage mode of the steel plate, the reliability verification of the numerical simulation, and the criterion for judging the damage mode of the steel plate were obtained. Results show that the damage mode of the steel plate changes with the changes in the explosive charge. The diameter of the crater on the surface of the steel plate is mainly related to the diameter of the contact surface between the explosive and the steel plate. The fracture mode of the steel plate in the process of generating cracks is a quasi-cleavage fracture, and the process of generating craters and perforations in the steel plate is a ductile fracture. The damage mode of the steel plates can be divided into three types. The numerical simulation results have minor errors and high reliability, and numerical simulation can be used as an auxiliary tool for experiments. A new criterion is proposed to predict the damage mode of the steel plates under contact explosion.

Effects of Pipeline Pressure on Diffusion Characteristics of Leaked Natural Gas in Tunnel Space.

Pipeline transportation has become the main mode of natural gas transportation. Due to inevitable aging, corrosion, and third-party damage, natural gas pipeline leakage accidents occur frequently. Leakage in the tunnel will lead to the leakage and accumulation of natural gas, and the potential explosion risk will threaten the tunnel's safety. It is significant to elaborate on the diffusion behavior of leaked natural gas in tunnel space for the traceability of leakage points and the formulation of safety technical measures. In this paper, a scale-down experimental platform for natural gas pipeline leakage in the tunnel is built, and the influence of pipeline pressure on natural gas diffusion characteristics is described. The results show that the diffusion process of leaked natural gas in the tunnel space shows obvious segmentation characteristics, and the concentration of natural gas reaches the maximum at the end of the continuous leakage stage. The increased pipeline pressure promotes natural gas diffusion, and the concentration of natural gas under 1.0 and 1.2 MPa rises sharply. First dangerous time (FDT) and maximum accumulated concentration (MAC) have a negative correlation with the leakage distance, while FDT and MAC have a good exponential and linear relationship with the pipeline pressure (0.2-1.2 MPa), respectively.

Buyang Huanwu decoction alleviates oxidative injury of cerebral ischemia-reperfusion through PKCε/Nrf2 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke is a significant risk factor for human health, and Buyang Huanwu Decoction is a classical and famous Chinese formula for treating it, but without clear pharmacological mechanism. AIM OF THE STUDY: The aim of this study was to investigate that the molecular mechanism of BYHWD activation of the PKCε/Nrf2 signaling pathway to attenuate cerebral ischemia-reperfusion (I/R) oxidative damage. MATERIALS AND METHODS: The MCAO method was used to establish a brain I/R injury model in SD rats, and neurological deficits were evaluated by neurological function score. Neuronal damage was observed by Nissl staining and immunofluorescence detection of MAP2 expression. Oxidative damage was observed by ROS, SOD, GSH-PX, MDA, and 8-OHdG. Changes in mitochondrial membrane potential were detected by using the fluorescent probe JC-1. The Western blot analysis detected protein expression of PKCε, P-PKCε, total Nrf2, nuclear Nrf2, HO-1, and NQO1. RESULTS: BYHWD significantly enhanced neural function, reduced neuronal damage, inhibited the production of ROS, decreased MDA and 8-OHdG levels, increased SOD and GSH-PX activity to reduce oxidative damage, and restored mitochondrial membrane potential. BYHWD and Nrf2 activator TBHQ increased total Nrf2, nucleus Nrf2 protein expression, and its downstream HO-1 and NQO1 proteins, and the administration of the Nrf2 inhibitor brusatol reduced the enhancing effect of BYHWD. Meanwhile, BYHWD increased the expression of PKCε and P-PKCε and the administration of the PKCε inhibitor εV1-2 reduced the effect of BYHWD in increasing the expression of PKCε, P-PKCε, nuclear Nrf2, and HO-1, as well as promoting the effect of Nrf2 translocation to the nucleus. CONCLUSION: This study marks the first to demonstrate that BYHWD ameliorates oxidative damage and attenuates brain I/R injury by activating the PKCε/Nrf2/HO-1 pathway.

Experimental and Numerical Study of Natural Gas Leakage and Explosion Characteristics.

Frequent occurrence of indoor natural gas explosion accidents seriously threatens the safety of people and property. To determine the law of indoor natural gas leakage and explosion hazards, based on experiment and simulation, the nature of natural gas explosion, the distribution law of natural gas volume fraction, flame propagation, temperature, and shock wave overpressure were studied. The results show that the flame structure can be divided into three zones, i.e., preheat zone, reaction zone, and product zone. OH + CO ⇔ H + CO2 is the main exothermic reaction in the combustion process. The overall distribution law of natural gas volume fraction shows that the higher the position, the greater the volume fraction, and the closer the distance to the leak source at the same height, the greater the volume fraction, and the natural gas volume fraction of the hose falling off is the largest under different leakage conditions. The difference in the wrapping structure of the kitchen package has a significant impact on the diffusion distribution of natural gas. The flame development goes through five stages of ignition, slow burning, detonation, slow burning, and extinguishing. The indoor temperature reaches about 1400 °C. Although the simulated value of shock wave overpressure is larger than the experimental value, the relationship between overpressure and distance is expressed by Y = A + B * ln(X + C). This study can provide certain technical support for natural gas accident rescue. The research can provide certain technical support for natural gas accident rescue and can also be used for accident investigation to form the determination procedure and method of leakage location and leakage amount.

Highly expressed miR-504 in gastric cancer tissues regulates the biological behaviors of gastric cancer cell BGC-823 through TP53INP1 / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探究微小RNA-504（miRNA-504）在胃癌（GC）组织中的表达水平及其对GC细胞生物学行为的调控机制。方法：收集2020年6月至2020年12月期间三亚中心医院外科收治的48例胃癌患者的肿瘤组织及癌旁组织标本，qPCR检测组织中miR-504、肿瘤蛋白53诱导型核蛋白1（tumor protein 53-induced nuclear protein 1，TP53INP1）mRNA的水平，WB法检测TP53INP1水平。体外培养人胃癌细胞BGC-823，分为对照组（正常培养的BGC-823细胞）、miR-504 mimic组、mimic-NC组、miR-504 inhibitor组、inhibitor-NC组、miR-504 inhibitor+si-NC组、miR-504 inhibitor+si-TP53INP1组，qPCR检测细胞中miR-504和TP53INP1 mRNA的表达，MTT法、流式细胞术、划痕实验和Transwell侵袭实验分别检测各组细胞的增殖、凋亡、迁移和侵袭能力，WB法检测各组细胞中增殖、迁移和侵袭相关蛋白（Cyclin D1、E-cadherin、MMP-2、MMP-9）以及TP53INP1的表达。双荧光素酶报告基因实验进一步验证miR-504与TP53INP1 mRNA的靶向关系。结果：与癌旁组织相比，胃癌组织中miR-504的表达显著升高（P<0.05），而TP53INP1 mRNA和蛋白表达水平显著降低（P<0.05或P<0.01），miR-504和TP53INP mRNA两者的表达呈负相关（P<0.01）。与对照组相比，miR-504 mimic组BGC-823细胞中miR-504的表达显著升高（P<0.05）、TP53INP1 mRNA和蛋白的表达显著降低（均P<0.05），且细胞增殖率、划痕愈合率、侵袭入Transwell小室下层的细胞数量，Cyclin D1、MMP-2、MMP-9蛋白表达均显著增加，细胞凋亡率和E-cadherin蛋白表达均显著降低（均P<0.05）。转染miR-504 inhibitor能显著下调BGC-823中miR-504的表达、上调TP53INP1 mRNA和蛋白的表达，抑制细胞的增殖、迁移与侵袭能力而促进细胞凋亡（均P<0.05）；而下调TP53INP1的表达可明显减弱miR-504下调对BGC-823细胞增殖、迁移与侵袭的抑制作用（P<0.01）。miR-504高表达能明显抑制野生型TP53INP1质粒的荧光素酶活性（P<0.05）。结论：miR-504在胃癌组织中呈高表达，下调miR-504可抑制胃癌BGC-823细胞的恶性生物学行为而促进其凋亡，其作用机制可能与靶向调控TP53INP1的表达有关。

Preparation of an Intelligent Oleophobic Hydrogel and Its Application in the Replacement of Locally Damaged Oil Pipelines.

In the pipeline transportation process for crude oil, the most important and popular maintenance method for perforated and ruptured oil pipelines is the replacement of the damaged pipeline segment. However, this method has several disadvantages, including a complex process, large time consumption, and excessively high costs. The present study reported the preparation of a strong cross-linking hydrogel that served as a temporary blocking material during the long-distance oil pipeline partial replacement process. The prepared product was characterized by infrared spectroscopy, X-ray diffraction analysis, and scanning electron microscopy to analyze the microscopic reactions and structures. Orthogonal experiments for shear stress were performed to determine the optimal synthesis condition. The relevant experiments indicated that the proposed product can effectively isolate oil and oil gas, and a 4.5 m long hydrogel can resist the force of a 0.57 MPa overpressure. The blocked pipeline turned to a dredged state on changing the pipeline pressure. The flame resistance experiment showed that the hydrogel exhibited excellent flame resistance and could therefore ensure the safety of the hot work. On the basis of this hydrogel material, a new method for replacing the partially damaged oil pipeline was proposed.

Synthesis and performance characterization of an efficient coal dust suppressant for synergistic combustion with coal dust.

Coal dust diffusion during coal transportation and storage causes serious environmental pollution. The existing dust suppressant in previous studies was unable to achieve the expected effects owing to severe wind damage and rain erosion. Therefore, the current study synthesized and prepared an efficient and applicable dust suppressant for coal transportation and storage. Infrared spectroscopy and scanning electron microscope experiments were conducted during the synthesis to analyze the microstructure changes in the synthetic products. Moreover, viscosity was used as the evaluation index in the single-factor experiments to obtain the optimal synthesis conditions. Performance measurement results showed that the prepared dust suppressant had a strong protective effect on coal powder and could effectively resist the impact of wind damage and rain erosion. Compared with other dust suppressants, the proposed dust suppressant prepared showed more evident positive effects and longer lasting action time in the quantitative test. Moreover, the dried product could synergistically combust with coal powder, thereby possibly mitigating the tedious post-treatment process and increasing the utilization rate of resources.

ErCas12a CRISPR-MAD7 for Model Generation in Human Cells, Mice, and Rats.

MAD7 is an engineered class 2 type V-A CRISPR-Cas (Cas12a/Cpf1) system isolated from Eubacterium rectale. Analogous to Cas9, it is an RNA-guided nuclease with demonstrated gene editing activity in Escherichia coli and yeast cells. Here, we report that MAD7 is capable of generating indels and fluorescent gene tagging of endogenous genes in human HCT116 and U2OS cancer cell lines, respectively. In addition, MAD7 is highly proficient in generating indels, small DNA insertions (23 bases), and larger integrations ranging from 1 to 14 kb in size in mouse and rat embryos, resulting in live-born transgenic animals. Due to the different protospacer adjacent motif requirement, small-guide RNA, and highly efficient targeted gene disruption and insertions, MAD7 can expand the CRISPR toolbox for genome enginnering across different systems and model organisms.

A Novel BCL-2 Inhibitor APG-2575 Exerts Synthetic Lethality With BTK or MDM2-p53 Inhibitor in Diffuse Large B-Cell Lymphoma.

Despite therapeutic advances, the effective treatment for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) remains a major clinical challenge. Evasion of apoptosis through upregulating antiapoptotic B-cell lymphoma-2 (BCL-2) family members and p53 inactivation, and abnormal activation of B-cell receptor signaling pathway are two important pathogenic factors for DLBCL. In this study, our aim is to explore a rational combination of BCL-2 inhibitor plus Brutons tyrosine kinase (BTK) blockade or p53 activation for treating DLBCL with the above characteristics. We demonstrated that a novel BCL-2 selective inhibitor APG-2575 effectively suppressed DLBCL with BCL-2 high expression via activating the mitochondrial apoptosis pathway. BTK inhibitor ibrutinib combined with BCL-2 inhibitors showed synergistic antitumor effect in DLBCL with mean expression of BCL-2 and myeloid cell leukemia-1 (MCL-1) through upregulating the expression level of BIM and modulating MCL-1 and p-Akt expression. For p53 wild-type DLBCL with high expression of BCL-2, APG-2575 showed strong synergic effect with mouse double minute 2 (MDM2)p53 inhibitor APG-115 that can achieve potent antitumor effect and markedly prolong survival in animal models. Collectively, our data provide an effective and precise therapeutic strategy through rational combination of BCL-2 and BTK or MDM2p53 inhibitors for DLBCL, which deserves further clinical investigation.

Serum Apolipoprotein A-I Combined With C-Reactive Protein Serves As A Novel Prognostic Stratification System For Colorectal Cancer.

BACKGROUND AND OBJECTIVE: Noninvasive prognostic tools for colorectal cancer (CRC) are urgently needed. This study was designed to investigate the prognostic value of preoperative serum lipid and lipoprotein concentrations (including ApoA-I, Apo-B, HDL-C, LDL-C, TC and TG) and CRP levels retrospectively in CRC patients. METHODS: Preoperative serum lipid and lipoprotein concentrations (including ApoA-I, Apo-B, HDL-C, LDL-C, TC and TG) and CRP levels were analyzed retrospectively in 250 patients with CRC. The prognostic significance of these indexes was determined by univariate and multivariate Cox hazard models. RESULTS: CRC patients with higher levels of ApoA-I and HDL-C and lower levels of CRP had significantly longer overall survival (OS, log rank test, p<0.05). Based on univariate analysis, ApoA-I levels (p=0.002), CRP levels (p=0.007), HDL-C levels (p=0.005), pT classification (p=0.005), pN classification (p<0.001), pM classification (p<0.001) and pTNM stage (p<0.001) were significantly associated with OS. Multivariate Cox proportional hazards regression analysis indicated that ApoA-I levels (HR: 1.52, p=0.023), CRP levels (HR: 1.85, p=0.035) and pTNM stage (HR: 2.53, p< 0.001) were independent predictors of CRC survival. The included patients were then stratified into three tiers based on the ApoA-I and CRP levels. In the whole cohort, the OS and disease-free survival differed significantly between the low-risk (ApoA-I≥1.08 mg/dL and CRP<3.04 mg/dL), medium-risk (ApoA-I≥1.08 mg/dL or CRP<3.04 mg/dL), and high-risk (ApoA-I<1.08 mg/dL and CRP ≥3.04 mg/dL) groups (p=0.001 and p=0.004). CONCLUSION: Decreased levels of ApoA-I and HDL-C and increased levels of CRP were predictive of poor prognosis among patients with CRC. In addition, the combination of ApoA-I and CRP can serve as a novel prognostic stratification system for more accurate clinical staging of CRC.

Correction: Tissue Specific Expression of Cre in Rat Tyrosine Hydroxylase and Dopamine Active Transporter-Positive Neurons.

[This corrects the article DOI: 10.1371/journal.pone.0149379.].

Experimental study on vented explosion overpressure of methane/air mixtures in manhole.

Gas explosion in manhole often occurs in cities. Many previous researches on gas explosion are not suitable for manhole explosion because of the particularity of manhole structure. To investigate the gas explosion in manhole, a full-scale manhole model was established, in which the explosion overpressure of methane/air mixtures were studied experimentally. The variation of blast wave overpressure with time at different distances was analyzed. In addition, the effects of methane concentration, ignition location and manhole cover weight on the external overpressure after manhole explosion were obtained. The results showed that at the experimental conditions in this paper, under the influence of vent mode and flame propagation, the maximum peak overpressure caused by manhole explosion was mostly at the third measuring point. And there were two peaks in the overpressure histories. It was also found that when the methane concentration was close to stoichiometric ratio, the ignition location was further away from the manhole head, and the weight of manhole cover increased, the peak overpressure of blast wave caused by explosion increased. Besides, some suggestions were put forward for the risk control of manhole explosion accident based on the experimental results.

Anchor Generation Optimization and Region of Interest Assignment for Vehicle Detection.

Region proposal network (RPN) based object detection, such as Faster Regions with CNN (Faster R-CNN), has gained considerable attention due to its high accuracy and fast speed. However, it has room for improvements when used in special application situations, such as the on-board vehicle detection. Original RPN locates multiscale anchors uniformly on each pixel of the last feature map and classifies whether an anchor is part of the foreground or background with one pixel in the last feature map. The receptive field of each pixel in the last feature map is fixed in the original faster R-CNN and does not coincide with the anchor size. Hence, only a certain part can be seen for large vehicles and too much useless information is contained in the feature for small vehicles. This reduces detection accuracy. Furthermore, the perspective projection results in the vehicle bounding box size becoming related to the bounding box position, thereby reducing the effectiveness and accuracy of the uniform anchor generation method. This reduces both detection accuracy and computing speed. After the region proposal stage, many regions of interest (ROI) are generated. The ROI pooling layer projects an ROI to the last feature map and forms a new feature map with a fixed size for final classification and box regression. The number of feature map pixels in the projected region can also influence the detection performance but this is not accurately controlled in former works. In this paper, the original faster R-CNN is optimized, especially for the on-board vehicle detection. This paper tries to solve these above-mentioned problems. The proposed method is tested on the KITTI dataset and the result shows a significant improvement without too many tricky parameter adjustments and training skills. The proposed method can also be used on other objects with obvious foreshortening effects, such as on-board pedestrian detection. The basic idea of the proposed method does not rely on concrete implementation and thus, most deep learning based object detectors with multiscale feature maps can be optimized with it.