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Objective:To obtain the relative biological effectiveness (RBE) of DNA double strand breaks (DSB) clusters by tracing the mechanism of radiated DNA damage, and explore the relationship among the biological effectiveness of DNA damage, chromosomal aberrations and germ cell death.Methods:Taking low-energy electrons, protons, and α particles as the research objects, this study simulated the process that cell nuclei were exposed to particle radiation using a radiation-related physicochemical model. On the ground of the DSB density-based spatial clustering of applications with noise (DBSCAN) algorithm, the DSB cluster classification method was improved to weaken the connection between the DSBs and the random distribution assumptions of energy depositions during the simulation. In this manner, the DSB clusters can be much closer to a non-random distribution. Furthermore, this study obtained the yields of DSB clusters and proposed a method to calculate the RBE values of DSB clusters.Results:The calculated RBE value (12.29) of DSB clusters of 2 MeV α particles was similar to the experimental RBE values of chromosomal fragments (15.3±5.9) and cell survival (14.7±5.1).Conclusions:After high-LET ionizing radiation, unlike the single DSB, the RBE of DSB clusters was similar to that of chromosomal aberration and cell survival.
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Nucleic acid drugs are highly applicable for cancer immunotherapy with promising therapeutic effects, while targeting delivery of these drugs to disease lesions remains challenging. Cationic polymeric nanoparticles have paved the way for efficient delivery of nucleic acid drugs, and achieved stimuli-responsive disassembly in tumor microenvironment (TME). However, TME is highly heterogeneous between individuals, and most nanocarriers lack active-control over the release of loaded nucleic acid drugs, which will definitely reduce the therapeutic efficacy. Herein, we have developed a light-controllable charge-reversal nanoparticle (LCCN) with controlled release of polyinosinic-polycytidylic acid [Poly(I:C)] to treat triple negative breast cancer (TNBC) by enhanced photodynamic immunotherapy. The nanoparticles keep suitably positive charge for stable loading of Poly(I:C), while rapidly reverse to negative charge after near-infrared light irradiation to release Poly(I:C). LCCN-Poly(I:C) nanoparticles trigger effective phototoxicity and immunogenic cell death on 4T1 tumor cells, elevate antitumor immune responses and inhibit the growth of primary and abscopal 4T1 tumors in mice. The approach provides a promising strategy for controlled release of various nucleic acid-based immune modulators, which may enhance the efficacy of photodynamic immunotherapy against TNBC.
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Non-alcoholic fatty liver disease (NAFLD) is characterized by increased fat depositions in the liver while the patients do not have drinking history.NAFLD has a prevalence of 10％ ～40％ in global,25％ ～26％ in Western populations.From 2004 to 2013,the numbers of new patients on the waitlist who had NASH increased by 170％ in America.The prevalence of NAFLD in China is 20％.With the decrease of HBV and HCV and the increase of diabetes mellitus type 2 and obesity,NAFLD will become the most common chronic liver disease in China over the next 20 years.NAFLD related end-stage liver disease will become the most common indication of liver transplantation.In this paper,the epidemiological features,pathogenesis,indication and prognosis of liver transplantation are reviewed.
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Macrophages are important innate immune cells that play essential roles in the inflammatory response. The phenotypic plasticity of macrophages enables them to be polarized into distinct gene phenotypes under different immune microenvironments to regulate the process of inflammation. The study of macrophage metabolic reprogramming aims to clarify the influence of key metabolic pathways on the regulation of different polarization states and related functions of macrophages. This review focuses on the relationship between the four key metabolic pathways [glycolysis, tricarboxylic acid (TCA) cycle, fatty acid metabolism and amino acid metabolism] and the distinct gene phenotypes of macrophages. It also reveals the metabolic regulation of the immune function of macrophage cells thus to provide new ideas and methods for the study of macrophage polarization-related process of inflammation.
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Objective To evaluate the effect of hypernatremia in donors on perioperative recovery of liver function in the recipients undergoing liver transplantation. Methods Clinical data of 73 liver transplant recipients were analyzed retrospectively. According to the serum levels of sodium in donors, all recipients were divided into hypernatremia group (donor serum sodium ≥150 mmol/L, n=19) and non-hypernatremia group (donor serum sodium < 150 mmol/L, n=54). Serum alanine aminotransferase(ALT), aspartate aminotransferase (AST), model for end-stage liver disease (MELD) score, albumin, total bilirubin (TB), serum creatinine, prothrombin time and hepatocyte growth factor (HGF) in the recipients were detected at 1, 3, 7, 14 and 21 d after liver transplantation. The time of postoperative use of liver-protecting drugs in the recipients, the length of intensive care unit (ICU) stay, the average length of hospital stay and the incidence rate of postoperative complications were statistically compared and analyzed. Results Compared with the non-hypernatremia group, the serum levels of TB, ALT, AST, HGF and MELD scores of the recipients in the hypernatremia group at the postoperative 1, 3 and 7 d were significantly higher (all P < 0.05), whereas the serum albumin level was significantly decreased (P < 0.05). The prothrombin time in the hypernatremia group was significantly longer than that in the non-hypernatremia group at 3 and 7 d after operation (both P < 0.05). In the hypernatremia group, the time of postoperative use of liver-protecting drugs and the length of ICU stay were 9 (7-13) d and 11 (8-13) d, significantly longer than 4 (3-9) d and 7 (3-9) d in the non-hypernatremia group (both P < 0.05). The average length of hospital stay, serum creatinine level and incidence rate of postoperative complications did not significantly differ between two groups (all P>0.05). All recipients were recovered and discharged. Conclusions The hypernatremia in donors exert no significant effect on the perioperative liver function of the recipients, whereas it can prolong the postoperative recovery time of liver function of the recipients.
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Perioperative fluid therapy is an important part of anesthesia management.Its main purpose is to maintain the perfusion of organs and tissues,ensure the balance of oxygen supply and demand,protect the function of organs and promote the rapid recovery of patients.Underload or overload of perioperative fluid infusion can affect the prognosis of patients during thoracic surgery.It is the basis of fluid management to using appropriate methods to accurately monitor of hemodynamic parameters.Goal-directed fluid therapy (GDFT),with hemodynamic parameters as targets,maximizes perioperative stroke volume through fluid loading.It plays an important role in accelerating patient recovery and reducing hospital stay and has been widely used in clinical.This article will review the progress of perioperative fluid management characteristics and circulatory function monitoring methods in thoracic surgery in order to provide guidance for clinical work.
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Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days , with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC.
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The deoxyribonucleic acid (DNA) molecule damage simulations with an atom level geometric model use the traversal algorithm that has the disadvantages of quite time-consuming, slow convergence and high-performance computer requirement. Therefore, this work presents a density-based spatial clustering of applications with noise (DBSCAN) clustering algorithm based on the spatial distributions of energy depositions and hydroxyl radicals (·OH). The algorithm with probability and statistics can quickly get the DNA strand break yields and help to study the variation pattern of the clustered DNA damage. Firstly, we simulated the transportation of protons and secondary particles through the nucleus, as well as the ionization and excitation of water molecules by using Geant4-DNA that is the Monte Carlo simulation toolkit for radiobiology, and got the distributions of energy depositions and hydroxyl radicals. Then we used the damage probability functions to get the spatial distribution dataset of DNA damage points in a simplified geometric model. The DBSCAN clustering algorithm based on damage points density was used to determine the single-strand break (SSB) yield and double-strand break (DSB) yield. Finally, we analyzed the DNA strand break yield variation trend with particle linear energy transfer (LET) and summarized the variation pattern of damage clusters. The simulation results show that the new algorithm has a faster simulation speed than the traversal algorithm and a good precision result. The simulation results have consistency when compared to other experiments and simulations. This work achieves more precise information on clustered DNA damage induced by proton radiation at the molecular level with high speed, so that it provides an essential and powerful research method for the study of radiation biological damage mechanism.
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Algorithms , Computer Simulation , DNA , Radiation Effects , DNA Damage , Linear Energy Transfer , Monte Carlo Method , ProtonsABSTRACT
Aiming at the disadvantages of traditional direct aperture optimization (DAO) method, such as slow convergence rate, prone to stagnation and weak global searching ability, a gradient-based direct aperture optimization (GDAO) is proposed. In this work, two different optimization methods are used to optimize the shapes and the weights of the apertures. Firstly, in order to improve the validity of the aperture shapes optimization of each search, the traditional simulated annealing (SA) algorithm is improved, the gradient is introduced to the algorithm. The shapes of the apertures are optimized by the gradient based SA method. At the same time, the constraints between the leaves of multileaf collimator (MLC) have been fully considered, the optimized aperture shapes are meeting the requirements of clinical radiation therapy. After that, the weights of the apertures are optimized by the limited-memory BFGS for bound-constrained (L-BFGS-B) algorithm, which is simple in calculation, fast in convergence rate, and suitable for solving large scale constrained optimization. Compared with the traditional SA algorithm, the time cost of this program decreased by 15.90%; the minimum dose for the planning target volume was improved by 0.29%, the highest dose for the planning target volume was reduced by 0.45%; the highest dose for the bladder and rectum, which are the organs at risk, decreased by 0.25% and 0.09%, respectively. The results of experiment show that the new algorithm can produce highly efficient treatment planning a short time and can be used in clinical practice.
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Objective: To discuss the protective effect of velvet antler polypeptides (VAP) combined with Schwann cells (SCs) modified by glial cell line derived neurotrophic factor (GDNF) gene on the apoptosis of spinal cord neurons induced by beta-amyloid 25-35 (Aβ25-35). Methods: The spinal cord cells of fetal mice were prepared and the spinal cord neurons in logarithmic growth phase were taken; the apoptosis of spinal cord neurons was induced by Aβ25-35. The spinal cord neurons were divided into normal cell group (the normal spinal cord neurons), induced apoptosis group (the apoptotic spinal cord neurons induced by Aβ25-35, SCs group (the apoptotic spinal cord neurons induced by Aβ25-35 + SCs), GDNF group (the apoptotic spinal cord neurons induced by Aβ25-35 + GDNF), SCs + GDNF group (the apoptotic spinal cord neurons induced by Aβ25-35 + GDNF-transfected SCs) and VAP combination group (the apoptotic spinal cord neurons induced by Aβ25-35 + VAP combined with GDNF-transfected SCs). Flow cytometry was used to detect the apoptotic rates of spinal cord neurons in various groups; immunohistochemical staining was used to detect the number of caspase-3 positive cells in the spinal cord neurons in various groups. Results; After suspension inoculation of fetal spinal cord neurons, most of them were round at the initial stage. The flow cytometry results showed that compared with induced apoptosis group, the apoptotic rates of spinal cord neurons in SCs, GDNF, SCs + GDNF, and VAP combination groups were decreased (P<0.05). Compared with SCs + GDNF group, the apoptotic rate of spinal cord neurons in VAP combination group was decreased (P<0. 05). The immunohistochemistry results showed that the expression of caspase-3 in spinal cord neurons in various groups could be found. There were no significant differences in the number of caspase-3 positive cells and cell staining between SCs group, GDNF group and SCs + GDNF group; but the number of caspase-3 positive cells in SCs group, GDNF group and SCs + GDNF group were significantly higher than that in induced apoptosis group (P<0. 05). Conclusion: VAP combined with GDNF-transfected SCs has the protective effect on the apoptosis of spinal cord cells by reducing the expression of caspase-3 in spinal cord neurons.
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Objective To explore the differences between the employment quality of graduates ma-joring in Chinese medicine and the demand of employers for providing theoretical reference for improving the employment rate of students in Chinese medicine colleges and universities. Methods The questionnaire on the employment quality of graduates majoring in traditional Chinese medicine and the needs of employers was designed based on the interviews and literature review. The questionnaire contains the dimensions of knowledge, ability and professional accomplishment, with several observation points in each dimension. Each observation point is measured by Likert 5 points, with "5" being the most important and "1" the least important. During the 2017 campus recruitment period of Heilongjiang University of Traditional Chinese Medicine, 350 questionnaires were issued to the graduates and 312 valid questionnaires were collected through convenient sampling, while 228 questionnaires were issued to the employers and 195 valid were collected. The database was established by using Excel software and the independent sample t test was conducted by using SPSS 22.0. Results The differences between graduates and employers were statistically significant in academic performance, knowledge structure, internship experience, professional conformity, scientific crea-tivity, experience of student cadres, CET-4 & CET-6 certificate, physical and mental health, honesty and trustworthiness (t=9.016, P=0.022; t=9.498, P=0.000; t=2.303, P=0.031; t=11.000, P=0.000; t=6.815, P=0.000; t=2.208, P=0.035; t=3.565, P=0.041; t=3.066, P=0.005; t=4.441, P=0.036). Conclusion There is a gap between the employment quality of graduates majoring in traditional Chinese medicine and the demand of employers. Traditional Chinese medicine colleges and universities can improve the employment quality of graduates and promote their successful employment by accelerating the course integration reform, and strengthening the construction of school spirit and credit evaluation system.
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Objective:To investigate the effect of pilose antler polypeptide combined with Schwann cells modified by glial cell line-derived neurotrophic factor (GDNF)gene on the proliferation of human bone marrow mesenchymal stem cells (BMSCs)in vitro .Methods:According to the conventional method,the bone marrow (10 mL)was extracted from the healthy volunteers and was inoculated into the culture flask.The primary cultured cells were completely fused.The BMSCs were harvested at the 3rd generation and the cells were adjusted to 5 × 106 mL-1 . 4 μL GDNF gene modified Schwann cells was added into GDNF group,4 μL (10 mg· L-1 )PAP combined with GDNF gene modified Schwann cells was added into combination group,and only same amount of medium was added into control group.The proliferative activities,cell nuclear antigen (PCNA)levels and apoptotic rates of BMSCs in various groups were detected by enzyme-linked immunosorbent assay,ELISA method and Annexin Ⅴ-FIFC/PI cell apoptosis detection kit,respectively.Results:After primary culture for 48 h,most of the cells adhered to the wall,and the morphology of the cells changed into polygonal shape and few of them showed spindle.The passaged cells showed spindle spindle,the cells were confirmed as BMSCs,and all of them were non-hematopoietic stem cells.Compared with control group,the proliferative activities and the PCNA level of the BMSCs in GDNF group and combination group were increased (P <0.05)and the apoptotic rates were decreased (P <0.05);compared with GDNF group,the proliferative activity and the PCNA level of the BMSCs in combination group were increased (P < 0.05 )and the apoptotic rate was decreased (P < 0.05 ).Conclusion:PAP combined with Schwann cells modified by GDNF gene can promote the proliferation of human BMSCs in vitro .
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Targeting the common fact that colleges and universities of traditional Chinese medicine neglect management post practice,are lack of cutting-edge,cross-disciplinary and methodological courses,fail to reflect the traditional Chinese medicine's singularity and update courses slowly during the process of cultivating their graduate students,Heilongjiang University of Chinese Medicine innovates its culture system of graduate student in related major.It is also devoted to developing problem-based learning,introducing bitutor system,reforming course system,which may hopefully improve their graduate students' innovative thoughts and abilities,strengthen their innovative knowledge theory system to finally discover an appropriate reform model for the culture system which can be perfectly replicable.
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Objective:To study the expression of caveolin-1 in colorectal adenocarcinoma tissues and its correlation with microlymphatic vessel density (LMVD), and to investigate the clinical pathological prognostic significance of caveolin-1 and LMVD in patients with colorectal cancer.Methods:The expression of caveolin-1 and LMVD in 45 specimens of normal colorectal tissues, and 90 specimens of colorectal adenocarcinoma tissues were detected by immunohistochemistry technique. The correlation between their expression and the clinicopathologic features was analyzed. Muhivariable Cox regression was used to analyze the association between the laboratory indices and overall survival time.Results:The positive rates of caveolin-1 in colorectal adenocarcinoma tissues were significantly higher than those in normal colorectal tissues (P<0.01). LMVD in colorectal adenocarcinoma tissues were significantly higher than those in normal colorectal tissues (P<0.01). Mean LMVD in group with caveolin-1 positive was significantly higher than in that with caveolin-1 negative. The median survival time was 26.7 months. Cox regression analysis showed that the caveolin-1 expression, invation depth, lymph nodemetastasis, TNM stage, liver metastasis and LMVD were independent risk factors of overall survival time of patients with colorectal carcinoma. Conclusions:Caveolin-1 may contribute to the lymphangiogenesis in the tumor. During the occurrence and development of colorectal adenocarcinoma, there is a close relationship between the expression of caveolin-1 and lymphatic microvessel of tumor. Caveolin-1 expression and microlymphatic vessel density are significant prognostic value of colorectal carcinoma.
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In order to characterize a thermostable urate oxidase (Uox) from Microbacterium sp. strain ZZJ4-1, we cloned its gene (uox). The open reading frame of uox contained 894 base pairs and encoded a protein with 297 amino acids. Alignment of gene sequences indicated there was no obvious identity with the most reported uox and that 72% identity was found with uox from Arthrobacter globiformis. We inserted the gene into the plasmid pET-15b to construct an expression vector pET-15b-uox and got it induced expression in Escherichia coli BL21 (DE3). After the purification of the recombinant Uox by the HisBind column, we studied some properties of it. It was composed of subunits with a molecular mass of about 35 kDa. The optimal temperature and pH was 30 degrees C and pH 7.5. It was stable below 65 degrees C and from pH 8.5 to 11.0. The Km value was 0.22 mmol/L with the uric acid as the substrate. Ag+, Zn2+, CU2+ and SDS could totally inhibit its activity while Tween 20, Tween 80 and Triton X-100 had a slight promotion effect. The thermal stability of this enzyme was the most excellent among the reported recombinant Uox. Based on this property, it would be very useful in the application.
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Actinomycetales , Genetics , Amino Acid Sequence , Cloning, Molecular , Enzyme Stability , Escherichia coli , Genetics , Metabolism , Genetic Vectors , Genetics , Molecular Sequence Data , Recombinant Proteins , Genetics , Urate Oxidase , Genetics , MetabolismABSTRACT
We purified a sarcosine oxidase from Bacillus sp. strain BSD-8 isolated from soil. We purified the enzyme by ammonium sulfate precipitation, DEAE-cellulose, Toyopearl hydrophobic and Sephadex G-75 molecular sieve chromatography and characterized the purified sarcosine oxidase. This sarcosine oxidase was a flavin enzyme containing a noncovalently bound flavin with the subunit molecular mass of 51 kDa. The optimal temperature for this enzyme was 60 degrees C and it showed its highest activity at pH 8.5. It was stable in the pH range of 8.0-10.0 and at the temperature of 60 degrees C. Estimated by Lineveaver-Burk plots, the K(m) of the enzyme was 3.1 mmol/L. Ag+, Hg2+, SDS and Tween 80 dramatically inhibted the enzyme activity, whereas Tween 20 and Triton X-100 had no effect on enzyme activity. The thermostability of this enzyme was better than reported sarcosine oxidases, and it could be applied in enzymatic measuring of creatinine.
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Bacillus , Bacterial Proteins , Chemistry , Metabolism , Chemical Precipitation , Enzyme Stability , Sarcosine Oxidase , Chemistry , Metabolism , Soil MicrobiologyABSTRACT
How to select and organize the content of course is an important component in curriculum reform. The special part for medicine in medical physics has characteristics of medical college, and is essential. The integration of this part is difficulty in curriculum reform of medical physics. In detail, the corresponding part of physics for medicine is integrated into a topic, which followed the part of classical physics. We adopted the method of special-topic teaching. Based on teaching experiences and in combination with the practical condition of the medical college, this paper selects and recombines some course content for medicine from medical physics, which is adopted by five-year medical students. Furthermore, some teaching requirement and guidance suggestion are presented.
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This paper analyses the significance of applying investigating study to teaching practice of medical physics at present.It introduces the establishment of a research project of investigating study in medical physics and specific research methods.
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This paper analyzes current problems in teaching thermology in medical physics.It introduces some ideas for reforming the thermology teaching:reforming traditional structure and system of its contents and improving teaching methods.
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In order to effectively and smoothly conduct an assessment of students' study in medical physics,it is necessary to design the assessment criteria for enhancing students' development in medical physics study.This paper deals with the construction of the assessment system and the design of the assessment criteria for evaluating students' study in the education of medical physics.