1.Research progress of nano delivery system in mRNA tumor vaccines
Pan-pan GU ; Tong GAO ; Yong-jun LIU ; Na ZHANG
Acta Pharmaceutica Sinica 2022;57(8):2327-2333
Tumor vaccine is one of the most promising therapeutic strategies in tumor immunotherapy. It promotes the antigen presentation process by delivering tumor antigen and then activates the anti-tumor immune response. As a new class of vaccines, messenger RNA (mRNA) vaccines can activate the immune system to achieve the purpose of immunotherapy by delivering the mRNA sequence of a specific antigen into the body and expressing the corresponding antigen protein. Compared with traditional vaccines, mRNA vaccines have the advantages of a short production cycle, high effectiveness, and strong immunogenicity. In recent years, the application of mRNA vaccines in tumor immunotherapy has attracted widespread attention, but the instability and low delivery efficiency of mRNA limit its application. Nano delivery system can effectively solve the problem of mRNA vaccine delivery, greatly promote the research process and clinical application of mRNA tumor vaccines, and has become a hot spot in the research of mRNA vaccines. In this review, we introduced the mRNA tumor vaccines, focusing on the application of nano delivery system in mRNA tumor vaccines, in order to provide new ideas and new methods for the efficient delivery of mRNA tumor vaccines and tumor immunotherapy.
2.Protective effect of dexmedetomidine on mechanically ventilated patients with pulmonary contusion
Jie XU ; Mingyuan MA ; Yong PAN ; Yinghua SONG ; Na YU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2014;(3):225-228
Objective To approach the protective effect of dexmedetomidine on mechanically ventilated patients with pulmonary contusion. Methods A prospective randomly controlled trial was conducted. 70 mechanically ventilated patients with pulmonary contusion from January 2010 to December 2012 in the Critical Care Medicine of Foshan Hospital of Traditional Chinese Medicine were divided into a control group and a therapy group by the difference in number odd or even,with 35 patients in each group. Based on the same principles of comprehensive treatment,the control group used midazolam,and the therapy group used dexmedetomidine for sedation. The measured parameters included oxygenation index(PaO2/FiO2),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6), and extra-vacular lung water index(EVLWI)for both groups on the1st and 5th day. The incidence of delirium,the time of mechanical ventilation,and the incidence of hypotension were observed in both groups. Results Compared with those on the 1st day,TNF-α,IL-6 and EVLWI on the 5th day were decreased significantly in both groups〔the control group TNF-α(ng/L):1.29±0.38 vs. 2.21±0.37,IL-6(ng/L):97.97±28.77 vs. 131.03±41.52,EVLWI (mL/kg):8.25±2.03 vs. 11.96±3.36;the therapy group TNF-α:1.06±0.33 vs. 2.32±0.37,IL-6:82.07±23.35 vs. 134.98±64.25, EVLWI(mL/kg):6.74±1.33 vs. 11.23±2.78, all P<0.05〕, PaO2/FiO2 was increased obviously〔mmHg(1 mmHg=0.133 kPa),the control group:285.80±30.65 vs. 213.00±33.70,the therapy group:315.00±34.50 vs. 229.50±37.00,both P<0.05〕,TNF-αand IL-6 had no significant difference compared between the therapy group and control group(TNF-α:1.06±0.33 vs. 1.29±0.38,IL-6:82.07±23.35 vs. 97.97±28.77), while EVLWI and PaO2/FiO2 in the therapy group had remarkable differences compared with those of the control group〔EVLWI(mL/kg):6.74±1.33 vs. 8.25±2.03,PaO2/FiO2(mmHg):315.00±34.50 vs. 285.80±30.65,both P<0.05〕. The incidence of delirium(8.57% vs. 22.86%)and time of mechanical ventilation(day:4.10±1.09 vs. 6.88±1.66)in the therapy group were decreased markedly compared with those of the control group,and the incidence of hypotension had no significant difference between treatment or control groups(17.14% vs. 14.29%,P>0.05). Conclusion Dexmedetomidine has protective effect on mechanically ventilated patients with pulmonary contusion, and it is an relatively ideal sedative drug for these patients.
3.Research on the Cytotoxicity of the Heterogeneous Acellular Corneal Stromal Leaching Solution on the CHL Cells
Xianning LIU ; Yao WANG ; Xianghua XIAO ; Shiyin PAN ; Yong YIN ; Na AN ; Xiuping ZHU
Journal of Modern Laboratory Medicine 2016;(1):112-114
Objective To select the largest non-toxic leaching solution concentration through the experimental observation of the cytotoxicity of the ostrich acellular corneal stromal leaching solution to the Chinese hamster lung fibroblasts cells(CHL) for the further chromosome distortion experiment.Methods The leaching solution made from the ostrich acellular corneal stromal material was diluted with concentrate of 1 ∶ 2,1 ∶ 4 and the original concentration were used to culture with the CHL cells,the negative and positive control were also set up at the same time,to evaluate the impact on cell growth after 24 hour by MTT colorimetric method.Results The leaching solution diluted with 1∶4 was non-toxic,and could promote the growth of the cells.Conclusion Combined with the results of classification and cell morphological features,this cytotoxicity test can be used to screen the best benchmark non-toxic concentrations for the chromosome aberration test of the CHL cells.
4.The relationship between function and thrombosis formation of left atrium appendage assessed by transesophageal echocardiography in patients with nonvalvular atrial fibrillation
Xiao-Di YAN ; Tian-Gang ZHU ; Yong-Feng REN ; Qian DING ; Xin QUAN ; Xin WANG ; Yong-Mei PAN ; Hui-Qing ZHOU ; Song-Na YANG
Chinese Journal of General Practitioners 2005;0(11):-
Objective To explore the relationship between size,shape and function of the left atrium appendage (LAA) and its thrombosis in patients with atrial fibrillation (AF) by transesophageal echocardiography (TEE) to provide evidence for clinical risk assessment,prognosis evaluation and treatment guidance.Method Length,diameter,end-diastolic volume (EDV) and ejection velocity (PEV) of LAA were measured in 41 patients with AF,and thrombus in LAA was detected by TEE.Results Thrombus in LAA was detected in seven of 41 patients of AF (17%).No significant difference in size and EDV was found between the patients with and without thrombus,but there was significant difference in PEV between them (P
5.SFRP5 gene silencing promotes proliferation and migration of human pancreatic cancer cell line PANC-1
rui Bao LIU ; na Yong WU ; ping Hai WANG ; Hui ZHANG ; guo Jian PAN ; ce Wen ZHOU
Basic & Clinical Medicine 2017;37(10):1434-1439
Objective To investigate the effect of lentivirus-mediated shRNA silencing SFRP5 on proliferation,in-vasion and migration of pancreatic cancer cell line PANC-1. Methods A SFRP5-knockdown recombinant plasmid was constructed and successfully transfected it into pancreatic cancer cell line PANC-1,blank plasmid transfection was treated as negative control and untreated cells as blank control group. The expression of SFRP5 at RNA and protein level in cell were detected by real-time PCR and Western blot, CCK-8 assay was applied to examine the effect of SFRP5 silencing on the proliferation, the cell migration of pancreatic cancer cell line PANC-1 was ana-lyzed by Transwell migration assay and cell scratch test was used to examine the cell invasion in PANC-1 cell. Results Stable transfected shRNA-SFRP5 cell of pancreatic cancer line was established successfully.The prolifera-tion capacity of SFRP5 group was significantly higher as compared to the negative control and blank control group by CCK8 assay(P<0.01).Similarly, cell invasion and migration of SFRP5 group were significantly higher compared to the negative control and blank control group(P<0.01). Conclusions SFRP5 lentiviral interference vectors can effectively decrease SFRP5 gene expression in PANC-1 cell of pancreatic cancer, thereby promoting cell proliferation,invasion and migration.
6.SFRP5 gene silencing promotes proliferation and migration of human pancreatic cancer cell line PANC-1
rui Bao LIU ; na Yong WU ; ping Hai WANG ; Hui ZHANG ; guo Jian PAN ; ce Wen ZHOU
Basic & Clinical Medicine 2017;37(10):1434-1439
Objective To investigate the effect of lentivirus-mediated shRNA silencing SFRP5 on proliferation,in-vasion and migration of pancreatic cancer cell line PANC-1. Methods A SFRP5-knockdown recombinant plasmid was constructed and successfully transfected it into pancreatic cancer cell line PANC-1,blank plasmid transfection was treated as negative control and untreated cells as blank control group. The expression of SFRP5 at RNA and protein level in cell were detected by real-time PCR and Western blot, CCK-8 assay was applied to examine the effect of SFRP5 silencing on the proliferation, the cell migration of pancreatic cancer cell line PANC-1 was ana-lyzed by Transwell migration assay and cell scratch test was used to examine the cell invasion in PANC-1 cell. Results Stable transfected shRNA-SFRP5 cell of pancreatic cancer line was established successfully.The prolifera-tion capacity of SFRP5 group was significantly higher as compared to the negative control and blank control group by CCK8 assay(P<0.01).Similarly, cell invasion and migration of SFRP5 group were significantly higher compared to the negative control and blank control group(P<0.01). Conclusions SFRP5 lentiviral interference vectors can effectively decrease SFRP5 gene expression in PANC-1 cell of pancreatic cancer, thereby promoting cell proliferation,invasion and migration.
7.Expression of SET-NUP214 fusion gene in patients with T-cell acute lymphoblastic leukemia and its clinical significance.
Hai-Ping DAI ; Qian WANG ; Li-Li WU ; Na-Na PING ; Chun-Xiao WU ; Jun-Dan XIE ; Jin-Lan PAN ; Yong-Quan XUE ; De-Pei WU ; Su-Ning CHEN
Journal of Experimental Hematology 2012;20(5):1047-1051
This study was aimed to investigate the occurrence and clinical significance of the SET-NUP214 fusion gene in patients with T-cell acute lymphoblastic leukemia (T-ALL), analyse clinical and biological characteristics in this disease. RT-PCR was used to detect the expression of SET-NUP214 fusion gene in 58 T-ALL cases. Interphase FISH and Array-CGH were used to detect the deletion of 9q34. Direct sequencing was applied to detect mutations of PHF6 and NOTCH1. The results showed that 6 out of 58 T-ALL cases (10.3%) were detected to have the SET-NUP214 fusion gene by RT-PCR. Besides T-lineage antigens, expression of CD13 and(or) CD33 were detected in all the 6 cases. Deletions of 9q34 were detected in 4 out of the 6 patients by FISH. Array-CGH results of 3 SET-NUP214 positive T-ALL patients confirmed that this fusion gene was resulted from a cryptic deletion of 9q34.11q34.13. PHF6 and NOTCH1 gene mutations were found in 4 and 5 out of 6 SET-NUP214 positive T-ALL patients, respectively. It is concluded that SET-NUP214 fusion gene is often resulted from del(9)(q34). PHF6 and NOTCH1 mutations may be potential leukemogenic event in SET-NUP214 fusion gene.
Carrier Proteins
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genetics
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Chromosome Deletion
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Chromosomes, Human, Pair 9
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genetics
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Gene Expression
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Histone Chaperones
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genetics
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Humans
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Mutation
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Nuclear Pore Complex Proteins
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genetics
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Oncogene Proteins, Fusion
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genetics
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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
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genetics
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Receptor, Notch1
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genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factors
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genetics
8.Number of lymph node metastases: a significant prognostic factor for patients with radical resection of carcinoma of the ampulla of Vater.
Ning LIU ; Han LIANG ; Ru-peng ZHANG ; Yuan PAN ; Yong LIU ; Jing-yu DENG ; Xiao-na WANG ; Xue-wei DING ; Xi-shan HAO
Chinese Journal of Gastrointestinal Surgery 2007;10(4):350-352
OBJECTIVETo identify prognostic factors predicting survival after radical resection of ampullary carcinoma.
METHODSClinical data of sixty- five patients with cancer of the ampulla of Vater underwent pancreaticoduodenectomy and regional lymphadenectomy were analyzed retrospectively.
RESULTSA total of 1380 lymph nodes dissected from the resected specimens was examined to detect the presence of metastasis. The median follow- up period was 83 months. Univariate analysis revealed that factors associated with poor survival included the number and the location of positive nodes. Thirty- three of the 65 patients had a total of 116 positive lymph nodes, of whom 20 had 1- 3 positive regional nodes lymph and 13 had > or = 4 positive regional lymph nodes. Multivariate analysis revealed that the number of positive nodes lymph was an independent prognostic factor (P=0.007), while the locations of lymph nodes failed to remain as an independent variable. The survival rate in patients with > or = 4 positive lymph nodes was significantly lower than that in those with 1- 3 positive lymph nodes. The median survival time was 49 months with a 5- year survival rate of 43% in patients with 1- 3 positive lymph nodes, whereas all patients with > or = 4 positive nodes died of the disease within 23 months after resection (P=0.0001).
CONCLUSIONThe number of positive regional lymph nodes is an independent prognostic factor in patients with ampullary carcinoma after resection.
Adult ; Aged ; Ampulla of Vater ; pathology ; Carcinoma ; pathology ; Common Bile Duct Neoplasms ; pathology ; Duodenal Neoplasms ; diagnosis ; secondary ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Postoperative Period ; Prognosis ; Retrospective Studies
9.Effect of hepatitis B virus X on the apoptosis of placental trophoblastic cells and its potential mechanism
min Wei WANG ; xing Yong YUAN ; Chen LI ; xia Yi PAN ; Na XU ; qin Gui BAI
Journal of Xi'an Jiaotong University(Medical Sciences) 2017;38(6):809-814
Objective To investigate the effect of hepatitis B virus X (HBx)protein on the apoptosis of placental trophoblastic cells and its potential mechanism.Methods A pcDNA3.1 expression vector of HBx gene was constructed and transfected into JEG-3 and HTR-8 human placental trophoblastic cell lines,respectively.After transfection for 48 h,RT-PCR and immunofluorescence analyses were made to detect HBx mRNA and protein expressions.Flow cytometry was used to detect the early apoptosis status of JEG-3 and HTR-8 cells.The expressions of PI3K and p-Akt were detected by immunofluorescence and Western blotting.Results After transfection for 48 h,RT-PCR and immunofluorescence analyses showed that HBx mRNA and protein expressions were detected in JEG-3 and HTR-8 cells.Flow cytometry revealed that early apoptosis of JEG-3 and HTR-8 cells was reduced by pcDNA-HBx transfection (P <0.05).Immunofluorescence and Western blotting showed that PI3K and p-Akt were significantly upregulated in HTR-8 cells (P < 0.05 ).Conclusion HBx gene can be transfected into JEG-3 and HTR-8 human placental trophoblastic cell lines,respectively.After the transfection,the early apoptosis of JEG-3 and HTR-8 cells is reduced.Its inhibition on apoptosis is related to the activation of the PI3K/Akt signaling path-way.
10.Expressions and activities of Rho GTPases in hypoxia and its relationship with tumor angiogenesis.
Yan XUE ; Feng BI ; Wen-chao LIU ; Yang-lin PAN ; Zhe-yi HAN ; Na LIU ; Chang-jiang LIU ; Hui-qin SHEN ; Xue-yong ZHANG
Chinese Journal of Oncology 2004;26(9):517-520
OBJECTIVETo study the expressions and activities of Rho GTPases in hypoxia and its relationship with tumor angiogenesis.
METHODSThree tumor cell lines were used in this study: gastric cancer cell lines AGS, SGC7901 and hepatocellular carcinoma cell line HepG2. Expression level of Rac1 mRNA was detected by semi-quantitative RT-PCR. Activity of Rac1 was determined by pull-down assay and expression of HIF-1alpha, VEGF, p53 and PTEN protein was detected by Westernblot.
RESULTSThe expression level of Rac1 mRNA was significantly increased in hypoxia compared to normoxia. Pull-down assay showed that hypoxia-induced activity of Rac1 was elevated in a time-dependent manner and climaxed at 3 hours. The expressions of HIF-1alpha and VEGF protein were up-regulated, while those of PTEN and p53 protein were down-regulated.
CONCLUSIONThese results indicate that hypoxia enhances Rac1 expression which might be involved in tumor angiogenesis by reacting with hypoxia-responsive genes.
Cell Hypoxia ; Cell Line, Tumor ; Hepatoblastoma ; blood supply ; metabolism ; pathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; biosynthesis ; genetics ; Liver Neoplasms ; blood supply ; metabolism ; pathology ; Neovascularization, Pathologic ; PTEN Phosphohydrolase ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Stomach Neoplasms ; blood supply ; metabolism ; pathology ; Tumor Suppressor Protein p53 ; biosynthesis ; genetics ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics ; rac1 GTP-Binding Protein ; biosynthesis ; genetics ; rho GTP-Binding Proteins ; biosynthesis ; genetics