BACKGROUND:The immunological rejection between host and graft is the leading cause of organ
transplantation failure. The traditional immunosuppressive agents have been unable to meet the needs of clinical treatment. Antibody-drug conjugate, as a type of new drugs, may be hope for the treatment of immune rejection. OBJECTIVE:To comprehensively analyze the composition of antibody-drug conjugates, mechanism of action, clinical research progress as wel as the development trend.
METHODS:A computer-based online retrieval was performed to search papers in CNKI and PubMed database using the key words of ADCs, immunosuppressive agents, immunotoxins, organ transplantation, graft rejection in Chinese and English. Recently published or published in the prestigious journals were selected in the same field. After excluding objective-independent papers and repeated studies, 42 papers were included for further analysis. RESULTS AND CONCLUSION:Antibody-drug conjugates, as highly effective and lowly toxic immunosuppressant, have achieved a breakthrough in treatment of targeting tumor, while the role of it in anti-immune rejection is stil at the exploratory stage. For islet transplantation, novel antibody-drug conjugates are required to block CD8+T effector by CD103/E-Cadherin pathway, and wil probably serve as a potential drug intervention for al ograft rejection.

Objective To prepare a kind of new lipid perfluorooctylbromide(PFOB) nanoparticles and to explore its potential application as an ultrasound contrast agent. Methods Lipid PFOB nanoparticles were prepared by microfluidization techniques. The morphology and distribution were observed with optical microscope and transmission electron microscope. Particle size and electric potential were determined with Malvern laser light scattering analyzer. Twelve normal Wistar rats were performed directly contrast imaging after injection of PFOB nanoparticles via caudal vein. Vital signs of the rats were monitored during the whole study. And eehogenie intensity of the liver was dynamically quantified through DFY ultrasound quantified analysis system. The mechanism of enhancement was studied by the frozen sections of rat's liver and spleen. Results The nanoparticles size and distribution were highly uniformed. The grey scale ultrasound imaging of the rat's liver and spleen were enhanced by PFOB nanoparticles. Ten seconds after PFOB nanoparticles injected,enhancement of liver began, the peak time was approximately 3 - 4 min, the duration of contrast enhancement was nearly up to 1 h, The enhancement of spleen was more significant and the duration was much longer. No abnormal changes of the rat's vital signs appeared during the study. Frozen sections suggested that PFOB nanoparticles accumulated in the liver and spleen was the potential mechanism of enhancement. Conclusions This novel and safe lipid PFOB nanoparticles could make prolonged enhancement of rat's liver and spleen,which has a good potency for ultrasound application.

Objective To evaluate the performance of virtual touch tissue quantification (VTQ)technique in noninvasive assessment of esophageal varices (EV) in patients with hepatitis B cirrhosis.Methods One hundred and thirty-five patients were enrolled in this study.Liver shear wave velocity (LSWV) and spleen shear wave velocity (SSWV) were obtained by VTQ technique,and the detection of EV was performed by upper endoscopy per patient.The severity of EV was staged on a G1-G3 scale.Liver function was also tested.ResultsThe mean value of LSWV in patients with cirrhosis was (2.48±0.50)m/s,LSWV was not correlated with the stage of EV.The mean value of SSWV was (3.25 ± 0.44) m/s,a significant,direct,linear correlation ( r =0.66,P＜0.001 ) was found between SSWV and the stage of EV.The cut-off value of SSWV for predicting the presence of EV was 3.16 m/s and the area under ROC curve was 0.83,with the sensitivity and specificity of 0.83 and 0.80,respectively.The cut-off value of SSWV for predicting severe EV was 3.39m/s and the area under ROC curve was 0.84,with the sensitivity and specificity of 0.83 and 0.77,respectively.ConclusionsIn cirrhotic patients infected with hepatitis B virus,SSWV measured by VTQ technique can be used as a noninvasive method for determining the presence and the severity of EV,however evidence to support a similar role for LSWV is lacking.

Objective To preparation a kind of Herceptin loaded and breast cancer targeted high molecular polymer ultrasound contrast agent and investigate their affinity for breast cancer in vitro. Methods The high molecular polymer PLGA-COOH ultrasound contrast agents were produced by the double emulsion technique. Herceptin was covalently linked to the PLGA-COOH nanoparticle surface using a carbodiimide technique. Its physical property was determined. The combination of Herceptin with the PLGA-COOH nanoparticle was proved by immunofluorescent assay,and the PLGA-COOH nanoparticle targeting specifity to breast cancer cells was observed with light microscope and confocal microscope,normal PLGA-COOH nanoparticle was served as control group. Results The diameter range of targeted high molecular polymer ultrasound contrast agents was 466.8～857.6 nm, the average diameter was (662.2 ± 69. 7) nm,85.9% of the diameter was in the range. Green punctiform fluorescence was observed by fluorescence microscope,and the conjugation of the targeted high molecular polymer ultrasound contrast agents with MCF-7 cells was tight while the conjugation in control group was negative. Conclusions The Herceptin loaded PLGA-COOH targeted ultrasound contrast agents was prepared successfully. The targeted ultrasound contrast agents can bind to breast cancer effectively in vitro.

Objective To prepare lipid-coated ultrasound microbubbles containing 10-HCPT(HLM) and explore the antitumor effects on mice xenografed H22 solid tumor using the technique of ultrasound-mediated HLM destruction. Methods Sixty-four tumor-bearing mice were radomly divided into A and B groups. Each group was divided into four groups again and administered respectively by tail vein with HI.M, non-drug-loaded microbubbles,10-HCPT and saline once a day. Ultrasound irradiation was applied on the tumor sites immediately after injection. After 7 days of consecutive treatment, all mice in group A were sacrificed and the tumors were harvested to measure weights. The tumor inhibition rate was calculated by weights. The tumor microvessel density (MVD) was detected by immunohistochemical staining. The tumor growth curve was depicted according to volumes. The survival time of mice in group B was recorded. Results The tumor inhibition rate was the highest in HLM group while this group's MVD was the lowest. Survival time in HLM group and 10-HCPT group were obviously longer compared with the control group,while no statistic difference was observed between the two groups. There was no statistic difference between the group of non-drug-loaded microbubbles and the control group. Conclusions Ultrasound irradiation mediates HLM destruction so that the drug is released from the vihicles at the same time, which can significantly enhance the tumor inhibition effect of 10-HCPT on the H22 tumor. This technique is expected to be adopted as a novel tool for liver cancer chemotherapy.

Purpose To study the expression of Ech1 in hepatocarcinoma and its clinical significance, and to explore the relationship between subcellular location of Ech1 and malignant biologic behaviour of hepatocarcinoma. Methods Immunohistochemical analysis was used to detect Ech1 expression in the 20 cases of normal liver tissue and the 30 cases of hepatocarcinoma. Subcellular location of Ech1 in Hca-F and FEch1-down cell was observed with subcellular protein extraction. Results The expression of Ech1 in primary hepa-tocarcinoma was increased compared to that of normal liver tissues ( P<0. 05 ) , while there was no significant difference between the expression of Ech1 with the age, AFP, and with or without liver cirrhosis or hepatitis virus in hepatocarcinoma (P>0. 05). Ech1 was found expressed almost at the same location although the expression level one is normal and the other is downregulation. Ech1 expres-sion was found in cytosol, membrane fraction, and its expression was higher in cytosol than other fractions both in Hca-F cell and Ech1 downregulated Hca-F cell. Conclusions The expression of Ech1 in primary hepatocarcinoma was increased, which may indicate that Ech1 is a critical factor in the development of primary hepatocarcinoma, but the subcellular location of Ech1 has not much contribution to that.

Acute lymphoblastic leukemia (ALL) is a highly heterogeneous disease. The prognosis of adolescents and adults with ALL is worse than that of children with ALL, mainly because of differences in biological characteristics. Molecular markers are of great value on risk stratification, prognosis evaluation, treatment guidance. The good news is with the deepening of studies on pathogenesis of ALL and the introduction of new technologies, novel molecular markers of prognostic relevance continue to be discovered. It was found that increased Sox4 expression was shown to correlate with accelerate leukemia progression. Unfortunately, resistance to medicine is associated with two cyclin-dependent kinase-inhibitor-2AB (CDKN2A/B) deletion.And the deletion of IKZF1 increase risk of relapse. Meanwhile, Ph-like acute lymphoblastic leukemia is characterized by a variety of genetic alterations that activate kinase or cytokine receptor signaling pathway. Identification of these molecular markers will provide important insights into the treatment strategies. This paper reviewed the advance in the Ph-positive ALL and Ph-like ALL.

By analyzing the questionnaire survey of consciousness of rights protection and status quo of rights and interests among medical staff in three 3rd degree and A grade hospitals located in northwest Hubei province,this paper concludes that medical staff there have a generally strong consciousness of rights,while their rights and interests are not well protected by society and hospitals,especially certain aspects including personal security,occupational health,working hours,legal vacation,and the rights to be involved in hospital management.It is suggested that legal rights and interests of medical staff should be improved through legislation,social support,and the direction function of public opinions.

We established a rapid detection method of New Delhi Metallo-beta-Lactamase Gene (NDM-1) based on Loop-mediated Isothermal Amplification (LAMP). With the application of LAMP, we designed four sets of LAMP premiers, using NDM-1 gene as the target sequence, and selected the set of optimal primers. Meanwhile, we established optimal reaction systems and conditions to carry out the sensitivity and specificity experiments. The experiment results showed that the whole detection process took only one hour and could be observed visually. In the experiment of sensitivity, NDM-1 gene had a detection limit of 6 copies in each reaction. In the experiment of specificity, we detected NDM-1 gene in 4 pathogen strains (Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae), and the total DNA from intestinal microbes and the total DNA from soil microbes. We had not detected the amplification reactions. The detection method established could rapidly detect NDM-1 gene and visualize the experiment result. The method is easy to operate and has high sensitivity and specificity and thus has great application value in basic research laboratories, emergent detection and spot detection.
Bacteria ; enzymology ; genetics ; Bacteriological Techniques ; methods ; DNA, Bacterial ; genetics ; Escherichia coli ; enzymology ; genetics ; Klebsiella pneumoniae ; enzymology ; genetics ; Nucleic Acid Amplification Techniques ; methods ; Sensitivity and Specificity ; Staphylococcus aureus ; enzymology ; genetics ; Streptococcus pneumoniae ; enzymology ; genetics ; beta-Lactamases ; genetics

Objective To study the effects of poly lacticoglycolic acid(PLGA) ultrasound contrast agent on tumor lymph node imaging and its mechanism.Methods PLGA ultrasound contrast agent was made by double emulsion method; VX2 tumor cells were harvested from carrier rabbits and inoculated in the thigh of healthy New Zealand White rabbits. Implants were allowed to grow for 14 to 18 days before imaging. Popliteal lymph nodes were imaged as the injection sites were massaged. And macrophages were used to investigate the mechanism for lymph node enhancement. Results PLGA ultrasound contrast agent had a tight size distribution. Tumor lymph node was significantly enhanced by PLGA ultrasound contrast agent. Macrophages experiment showed that macrophages could phagocyte lots of PLGA ultrasound contrast agents.Conclusions PLGA ultrasound contrast agent is good for lymph node imaging. The possible mechanism for lymph node enhancement is that macrophages in lymph node can phagocyte lots of PLGA contrast agents, which causes the concentration of PLGA contrast agent in lymph node.