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Cancer vaccines represent a promising immunotherapeutic treatment modality. The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex (MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects. Current vaccination strategies, however, are not able to achieve the spatiotemporal control of antigen cross-presentation. Here, we report a liposomal vaccine loading the second near-infrared window (NIR-II, 1000-1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance. The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes (DLNs). Moreover, the photothermally induced endolysosomal rupture initiates autophagy. We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/mTOR pathway. The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation. This study presents a paradigm of NIR-II image-guided light-triggered vaccination. The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.
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An essential step for cancer vaccination is to break the immunosuppression and elicit a tumor-specific immunity. A major hurdle against cancer therapeutic vaccination is the insufficient immune stimulation of the cancer vaccines and lack of a safe and efficient adjuvant for human use. We discovered a novel cancer immunostimulant, trichosanthin (TCS), that is a clinically used protein drug in China, and developed a well-adaptable protein-engineering method for making recombinant protein vaccines by fusion of an antigenic peptide, TCS, and a cell-penetrating peptide (CPP), termed an "all-in-one" vaccine, for transcutaneous cancer immunization. The TCS adjuvant effect on antigen presentation was investigated and the antitumor immunity of the vaccines was investigated using the different tumor models. The vaccines were prepared
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Objective To evaluate the clinical effect of emedastine difumarate eye drops combined with pranoprofen eye drops on histamine (HA), eosinophil cationic protein (ECP), leukotrienes B4(LTB4) and, IgE levels of allergic conjunctival and provide reference for clinical diagnosis and treatment.Methods 76 cases of patients with allergic conjunctivitis were randomly divided into control group and experimental group , control group were treated with fumaric acid emedastine eye drops, experimental group were treated with fumarate emedastine combined with pranoprofen eye drops, and then compare the efficacy and serum ECP, HA, LTB4 and IgE levels between two groups before and after treatment of the symptoms and signs score . Results The total efficacy of experimental group was significantly higher than that in control group (94.70%vs.81.60%)(P<0.05).The serum ECP, HA, LTB4 and IgE levels of experimental group were significantly lower than those in control group(P<0.05).Conclusion The emedastine difumarate combined with pranoprofen eye drops in the treatment of allergic conjunctivitis is better than single medication, and ECP, HA, LTB4, IgE significantly decrease.
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<p><b>OBJECTIVE</b>To observe the influence of different methods of moxibustion on spleen morphology in cyclophosphamide-induced immunosuppressive rabbits.</p><p><b>METHODS</b>A total of 50 rabbits were randomly assigned into a blank group, a model group, a herbal cake-separated moxibustion group, a moxibustion group and a sham cake-separated moxibustion group, 10 rabbits in each group. Except the blank group, the rabbits in each group were treated with intraperitoneal injection of cyclophosphamide (60 mg/kg), once a day, for 7 consecutive days to establish immunosuppressive model. After the model establishment, the rabbits in the herbal cake-separated moxibustion group were treated with herbal cake-separated moxibustion at "Shenque" (CV 8), "Guanyuan" (CV 4), "Zusanli" (ST 36), "Pishu" (BL 20) and "Shenshu" (BL 23); the moxa cone was placed on the herbal cake which was made ofdecoction, three cones for each acupoint. The rabbits in the moxibustion group were treated with moxa stick moxibustion which contained equal moxa of three moxa cones. The rabbits in the sham cake-separated moxibustion group were treated with cake which was made of flour. The acupoint selection in the above three groups was identical, and the intervention was given once every other day for totally 10 times. The rabbits in the blank group and model group were immobilized for identical time without any intervention. After treatment, the rabbits were sacrificed to collect the spleen. With routine HE staining, the morphology changes of spleen were observed under microscope. In addition, the white pulp, splenic corpuscle and the counts of lymphatic cells of lymphatic sheath around the arteries were observed.</p><p><b>RESULTS</b>Compared with the blank group, the average size of white pulp and the radius of splenic corpuscle were reduced (both<0.01), and the lymphatic cells of lymphatic sheath around the arteries were significantly decreased in the model group (<0.01), but the counts of splenic nodule were increased without significant difference (>0.05). Compared with the model group, the averagesize of white pulp and the radius of splenic corpuscle were significantly increased in the herbal cake-separated moxibustion group and moxibustion group (all<0.01). The lymphatic cells of lymphatic sheath around the arteries were significantly increased in the herbal cake-separated moxibustion group and sham cake-separated moxibustion group (both<0.01). Compared with the moxibustion group, the count of lymphatic cells of lymphatic sheath around the arteries was increased in the herbal cake-separated moxibustion (<0.01). Compared with the sham cake-separated moxibustion group, the radius of splenic corpuscle was significant increased in the herbal cake-separated moxibustion group (<0.01).</p><p><b>CONCLUSIONS</b>The improvement of herbal cake-separated moxibustion on immunologic function is superior to moxibustion and sham cake-separated moxibustion in cyclophosphamide-induced rabbits.</p>
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Objective To evaluate the correlation between the expression level of Nanog gene and clinical outcomes of GP regimen in the advanced non-small cell lung cancer (NSCLC).Methods 62 patients of NSCLC were treated by GP method,and the outcomes were investiged between Nanog positive and nagetive patients.The expression level of Nanong was evaluated by RT-PCR and immunohistology.Results 30 out of 62 patients (48.4 ％) were Nanog positive,9 patients (28.1％) were Nanog positive,and 23 out of 32 patients were Nanog negative (71.9 ％) who have the positive effect (CR+PR).However,among 32 treatment nagetive cases,there were 21 cases (70.0 ％) who were Nanog positive and 9 cases (30.0 ％) were Nanog negatve.Survival analysis showed that 5-years lifetime of Nanog positive patients was shorter than Nanong nagetive patients.Conclusion Nanog overexpression decreases the sensitivity of GP regimen and lifetime of NSCLC patient.Nanog expression level may provide a useful factor for clinical treatment and prognosis of NSCLC patient.
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ObjectiveTo explore the relationship between the expression of Dishevelled2 and Vangl2 and the embryonic neural tube defects (NTDs) induced by all-trans retinoic acid (RA)in Kunming mouse. Methods Fifty pregnant mice were randomly divided into control and RA-treated groups.RA-treated mice were fed with 30mg/kg RA dissolved with peanut oil on embryo 7.75 days, while the mice of control group were administrated with an equal volume of peanut oil on the same time. Then all the embryos were sampled from pregnant mice at the 4th, 18th, 42nd, 66th and 90th hour after treatment. In situ hybridization and immunohistochemical staining technique were used to detect the expression of Dishevelled2 and Vangl2 in embryonic neural tube. Results The two proteins both existed in the epithelial tissue of the mouse embryonic neural tube and displayed different expression modes at various developmental stages.Compared with the control group, the RA treated group showed a significant decrease (P≤0.05) at the 18th and 42nd hour and a significant increase (P≤0.05) at the 66th hour in Dishevelled2 protein after maternal treatment, and no significant difference was found at the 90th hour. Compared with the control group, the Vangl2 mRNA expression in the RA treated group displayed a significant decrease (P≤0.05) at the 4th and 18th hour and a significant increase (P≤0.05) at the 66th hour after RA treatment, and no difference was found at the 42nd hour. Compared with the control group, the expression of Vangl2 protein in the RA treated group decreased (P≤0.05) at the 18th and 42nd hour, and increased (P≤0.05) at the 90th hour after RA treatment, no difference was found at the 66th hour. Conclusion Excessive RA may interfere with the normal embryonic neural tube closure by regulating the expression of Dishevelled2 and Vangl2.
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Objective To study the association between paternal CD3, CD4 and CD8 antigenecity to their pregnant spouses and the development of pregnancy induced hypertension (PIH). Methods Maternal serum from 15 women with PIH in the third trimester and 82 in normal pregnancies (16 in the first, 32 in the second and 34 in the third trimester) were incubated with paternal T lymphocytes. Monoclonal CD3, CD4 and CD8 fluorescent conjugated antibodies were then added and the percentage of paternal T cell differentiation antigen CD3, CD4 and CD8 were measured by flow cytometry. Results During normal pregnancy, the levels of maternal serum blocking antibodies on paternal CD3, CD4 and CD8 were (4.14?1.02, 2.02 ?0.24, 2.37?1.05)% in first trimester, (-0.29?0.13, 1.03?0.27, 0.65?0.23)% in the second trimester and (-1.33?1.47,0.15?0.01, -1.04? 0.37)% in the third trimester. There were significant difference between them( P
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Objective To study the polymorphisms of the large mutiplefunctional protease (LMP2) genes in women with severe pre-eclampsia (S-PE) and the sharing rate of LMP 2 in these women and their partners and couples. Methods Totally, 102 S-PE women and their husbands were enrolled in the study group, and 200 normal pregnant women and their husbands as control. The types of LMP2 alleles were assessed by polymerase chain reaction-restriction fragment lengthpolymorphism method (PCR-RFLP) after PCR. Results The frequency of LMP2R/H in S-PE group was significantly higher than that of the control (53.9% vs 35.%, P