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Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.
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Objective:To propose a markless patient setup workflow based on the optical surface monitoring system (AlignRT) and open-face mask immobilization for whole-course head tumor radiotherapy, assess the setup time and repositioning frequency of the proposed workflow, and conduct a comparative analysis of the differences, correlation, and consistency of the setup errors of the AlignRT and cone beam CT (CBCT) systems.Methods:A retrospective analysis was conducted for the data on the errors of 132 fractionated setup based on open-face mask immobilization of 33 head tumor patients. AlignRT-guided markless patient setup workflow was applied throughout the radiotherapy. Meanwhile, the body structures automatically generated by the treatment planning system were used as body references. The 6-degree-of-freedom (6DoF) setup errors (lateral, vertical, longitudinal, rotation, pitch, roll, and yaw directions), setup time, and repositioning frequency of the AlignRT and CBCT systems were recorded and analyzed. The Wilcoxon and Spearman analyses were used to statistically assess the differences and correlation of the setup errors of the two systems. Moreover, the Bland-Altman analysis was employed to evaluate the consistency of the two systems.Results:The 6DoF setup errors of CBCT were within the clinical tolerance (linear motions: -0.30 to 0.30 cm; rotational motions: -2.0° to 2.0°). The setup time and repositioning frequency of CBCT were (98 ± 31) s and 1.51% (2/132), respectively. There was no significant difference in setup errors between the two systems except those in x-axis ( Z = -3.11, P= 0.002), y-axis ( Z = -7.40, P<0.001), and Pitch ( Z= -4.48, P<0.001). There was a significant positive correlation between the setup errors along lateral ( rs = 0.47, P<0.001) and vertical ( rs = 0.29, P = 0.001) directions, rotation (Rtn; rs = 0.47, P<0.001), pitch (Pitch; rs = 0.28, P = 0.001) and roll (Roll; rs = 0.45, P<0.001) of the two systems. The 95% limits of agreement (95% LoA) of 6DoF setup errors were -0.12 to 0.09 cm, -0.07 to 0.17 cm, -0.19 to 0.20 cm, -1.0° to 0.9 °, -1.0° to 1.5°, and -0.9° to 1.0°, respectively. The 95% confidence interval (95% CI) of 95% LoA was -0.14 to 0.11 cm, -0.09 to 0.19 cm, -0.23 to 0.23 cm, -1.2° to 1.1°, -1.2° to 1.7°, and-1.0° to 1.1°, respectively, all of which were within the permissible error ranges. The 6DoF setup error difference of 3.41% (27/792< 5%) was beyond the 95% LoA. The maximum absolute differences of 6DoF setup errors within the 95% LoA were 0.12, 0.16, 0.19 cm, 0.9°, 1.5°, and 1.0°, respectively. Conclusions:The proposed markless setup workflow based on AlignRT combined with open-face mask immobilization for whole-course head tumor radiotherapy exhibits reasonable agreement and consistency with the patient setup using CBCT, with acceptable clinical efficiency. It can be applied to the first radiotherapy and the real-time monitoring of therapy to improve the safety and thus is of value in clinical applications.
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Objective This systematic review and Meta-analysis was conducted to clarify the safety and efficacy of robotic-assisted (RP),laparoscopic (LP) and open (OP) dismembered pyeloplasty.Methods A systematic literature search on MEDLINE,Cochrane Central Register of Coutrolled Trials,and Web of Science was conducted to identify the relevant studies published before December 2018.Information was extracted from each eligible article.All statistical analyses of this Meta-analysis were performed with Stata 14 and RevMan 5.3 software.Results A total of 24 studies met the inclusion criteria and were included in this Meta-analysis.Compared with OP,LP showed similar results on success rate (OR =0.89,95 ％ CI 0.47-1.69,P =0.729) and complication rate (OR =0.89,95％ CI0.58-1.36,P =0.585).LP had a longer operative time(WMD =53.86,95％ CI 13.23-94.29,P =0.009) and shorter length of stay (WMD =-2.32,95％ CI-3.48--1.16,P ＜ 0.001).Our study found that RP was superior to LP with respect to success rate (OR =2.53,95 ％ CI 1.03-6.19,P =0.043),complication rate (OR =0.54,95 ％ CI 0.31-0.96,P =0.034),operative time (WMD =-25.94,95％ CI-47.56--4.23,P =0.019) and length of stay (WMD =-25.94,95％ CI-47.56--4.23,P =0.019).Conclusions RP has some advantages,it may be applied for UPJO routinely in the future if the costs can be decreased.
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Objective To explore the effects of electroacupuncture at Baihui (DU20) acupoint on learning and memory and its possible mechanism through the expression of brain-derived neurotrophic factor (BDNF) in APP/PS1 double-transgenic mice. Methods 30 female APP/PS1 double transgenic mice were randomly divided into model group, DU20 group and non-acupoint group, and 10 wild type mice con-sisted of wild group. DU20 group received electroacupuncture at Baihui and the non-acupoint group received electroacupuncture at non-acu-point for 28 days. Learning and memory was tested by Morris water maze. Deposition ofβ-amyloid (Aβ) peptide was determined by immu-nohistochemical staining. The expression of BDNF in cortex was examined by RT-PCR and Western blotting. Results Compared with the model group, DU20 group ameliorated the learning and memory ability of APP/PS1 double-transgenic mice (P0.05). Conclusion Electroacupuncture at DU20 acupoint could ameliorate learning and memory in APP/PS1 double-transgenic mice. The mechanism may be related to increase the expression of BDNF and decrease the deposition of Aβ.
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Aim To investigate the effect of resveratrol on astrocyte activation after cerebral ischemia/reperfusion injury in rats.Methods 45 male Sprague-Dawley rats were divided into sham,control and resveratrol groups, 15 rats in each group.Resveratrol or solvent was intra-peritoneally perfused into the rats for 7 consecutive days after 3h for MCA I /R.Cerebral infarction volume with TTC,neurological function score with Longa score, and pathological change with HE staining,the protein expressions of Caspase-3 with immunohistochemistry at 24h after MCA I /R were examined.The protein ex-pressions of GFAP and NeuN in penumbra were detec-ted with immunohistochemistry and immunofluores-cence at 14d after MCA I /R.Results Resveratrol treatment significantly improved the neurological func-tion score,decreased the infarct volume,reduced neu-ron loss,and inhibited the activation and proliferation of astrocytes,compared with the control group.Con-clusion Resveratrol can inhibit the excessive activa-tion of astrocytes,protect neurons in penumbra and im-prove neurological function.
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Cytokine induced killer (CIK) cells are a new kind of cytotoxic cells,which are generated by stimulation of peripheral blood mononuclear cells (PBMC) with IFN-γ,IL-2,IL-1 and anti-CD3 in vitro.These cells represent phenotype of both T cell and NK cell and have advantages of the non MHC restriction,so they have a strong ability of antitumor activity in vivo and vitro.Now,CIK cells as the main effector cells of adoptive immunotherapy have been extensively used in a variety of solid tumors such as liver cancer,lung cancer and hematological malignancies including leukemia,lymphoma,myeloma.In this article,the optimized cultivation of CIK cells as well as their most prominent clinical application in hematologic malignancies were summarized.
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Objective To discuss the therapeutic method of extracranial athemsclerotic carotid artery stenosis . Methods A retrospective analysis was conducted in 51 patients with angiography confirmed carotid artery stenosis from January 2012 to June 2012 in our hospital.The carotid endarterectomy (CEA) was performed in 16 cases, while the carotid artery stenting (CAS) was performed in 35 cases. Results All the 51 operations were successfully completed .There were 1 case of transient ischemic attack ( TIA) 3 days after CEA operation , 1 case of postoperative stroke after CAS operation , and 1 case of carotid sinus pressure after CAS operation . The follow-up period of all the cases was 9-15 months, with an average of 13.6 months.Ultrasound review of the carotid artery found no restenosis. Conclusion According to medical information of the patients with extracranial carotid atherosclerotic stenosis , we tend to adopt the CAS treatment in patients with following situations: ①transient ischemic attack at least once within 6 months, with symptoms or signs lasting for more than 24 hours and the degree of carotid stenosis ≥70%;②mild than disabling stroke onset at least once within 6 months, with symptoms or signs lasting for more than 24 hours and the degree of carotid stenosis ≥70%; ③carotid artery stenosis ≥2 cm under neck vascular CTA and cerebral angiography .We tend to adopt CEA treatment in patients with following situations:①asymptomatic carotid stenosis with degree ≥70%;②symptomatic carotid stenosis with degree range from 50%to 69%;③asymptomatic carotid artery stenosis with degree <70%, but with instable situation of lesions under angiography or other examinations .
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Objective To investigate the expressions of vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor-D (VEGF-D) and their relationship with lymph node metastasis in gastric cancer. Methods Eighty patients with gastric cancer had been admitted to our department from January 2005 to December 2005, including 48 with local lymph node metastasis and 32 without local lymph node metastasis. Ten specimens of normal gastric mucosa from patients with gastric ulcer were used as control. The expression of VEGF-C and VEGF-D in serum and tissues were detected. Results The senun levels of VEGF-C and VEGF-D in patients with gastric cancer were significantly higher than those in the control group (χ2= 8.39, P < 0.05). The positive rate of the VEGF-C expression in the sermn of patients with gastric cancer was influenced by the lymph node metastasis (χ2 = 7.01, P < 0.05). The positive rates of the expressions of VEGF-C and VEGF-D in the gastric cancer tissue were 53% (42/80) and 63% (50/80), which were significantly higher than those in the normal gastric mucosa (χ2 =6.44, 6.58, P <0.05). The positive rate of the VEGF-C expression in the tissue of patients with gastric cancer was influenced by the lymph node metastasis (χ2=11.25, P <0.05). Conclusions The expression of VEGF-C is closely related to lymph node metastasis of gastric cancer. The serum levels of VEGF-C can be used as biologic markers in detecting lymph node metastasis of gastric cancer preoperatively.
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Objective To study the effects of dendritic cells (DC) modified with transforming growth factor ?1 (TGF-?1) gene on experimental autoimmune myasthenia gravis (EAMG) in Lewis rats. Methods 30 female Lewis rats were divided randomly into 6 groups: normal group, EAMG group, DCs treatment group, pcDNA_3-TGF-?1-DCs treatment group, pcDNA_3-DCs treatment group and normal saline group. The rats were immunized with the acetylcholine receptor (AChR) protein extracted from electric organ of Narcine timilei and completed Freund’s adjuvant (CFA) in the experiment groups except normal group. 2?106 pcDNA_3-TGF-?1-DCs/rat were injected subcutaneously into the backs of the rats that had been immunized 5 days earlier with AChR+CFA. The rats in DCs treatment group, pcDNA_3-DCs treatment group and normal saline group were injected in parallel with untreated DCs, pcDNA_3-DCs and normal saline respectively. Then the clinical manifestations were observed everyday. And 7 weeks after the first immunization, repetitive nerve stimulation, detection of acetylcholine receptor antibody (AChRab) and ultrastructural study of neuromuscular junction (NMJ) were performed. Results (1) The mild symptoms were observed on 1 or 2 rats in the experiment groups except normal group after a week, which lasted for 2 to 5 days. After about 5 weeks, the rats in EAMG group, DCs treatment group, pcDNA_3-DCs treatment group and normal saline group presented some symptoms at different degree like myasthenia gravis, and only one of the rats in pcDNA_3-TGF-?1-DCs treatment group presented mildly decreased activity. (2) The significant decrement of repetitive nerve stimulation were found in EAMG group, DCs treatment group, pcDNA_3-DCs treatment group and normal saline group(16.75?6.13, 17.75?7.81, 18.25?8.22 and 16.50?7.14, respectively), but there was no attenuation in pcDNA_3-TGF-?1-DCs treatment group and normal group(3.20?3.70 and 5.60?2.70, respectively). The percentage of decrement in pcDNA_3-TGF-?1-DCs treatment group was lower than that in EAMG group(5.60?2.70 and 16.75?6.13, respectively,P0.05). (4) The combined AChRs in NMJ of the rats in pcDNA_3-TGF-?1-DCs group were higher than that in EAMG group, and the structure changes of the synapse were relieved.Conclusion It suggests that DCs, transfected with pcDNA_3-TGF-?1, when injected subcutaneously into Lewis rats with incipient EAMG, could inhibit the production of AChR-Ab, relieve the pathologic changes in NMJ and ameliorate the development of EAMG.