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Programmed death ligand-1 (PD-L1) is highly expressed on most tumor cells,and it interacts with programmed death-1 (PD-1) on the surface of immune cells,which mainly inhibits T cell proliferation and plays an important role in tumor immune escape.The studies find that PD-1/PD-L1 pathway can promote tumor cell glycolysis and epithelial-mesenchymal transition,and can induce PD-L1 expression on macrophages and enhance immunosuppression in tumor microenvironment.Therefore,PD-1/PD-L1 is considered to be an important immunoassay point,and a series of anti-PD-1 and PD-L1 antibodies,such as pembrolizumab,nivolumab,atezolizumab,durvalumab and avelumab,have clinically shown good effects.Further understanding of its mechanism may provide new ideas for the treatment of malignant tumors such as lung tumors.
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Objective@#To explore the effects of cigarette smoke exposure during pregnancy on the quality of oocytes and the whole genome DNA methylation in the offspring of female mice during the period of germinal vesicle (GV) .@*Methods@#The pregnant 7 d mice were divided into 3 groups, exposure on the 0, 0.5, 1 lit cigarettes cabinet (volume 18 L) , at 9 am and 3 pm for 1 h twice daily, until delivery. When the mice were 6 weeks old, the organ index and the number of follicles in the ovary were detected by weighing and making HE stained sections. GV stage oocytes were obtained by Hoechst 33342 staining and indirect immunofluorescence to detect the quality of oocytes, chromatin configuration and whole genome DNA methylation level.@*Results@#Compared with the control group and low dose group, the offspring ovarian organ index of female mice in the high dose group decreased, the difference was statistically significant (P<0.05) . Compared with the control group, the number of follicular oocytes in low dose group and high dose group female mice offspring decreased, the zona pellucida oocytes diameter decreased, and the zona pellucida thickness increased, the differences were statistical significance (P<0.05) . Compared with control group and low dose group, in the high dose group, the oocytes nucleus diameter of the female mice offspring decreased, the proportion of nucleolus surrounded type chromatin configuration (SN) decreased, and the proportion of nucleoil not surrounded type (NSN) increased, the relative fluorescence intensity of 5MeC decreased, the differences were statistically significant (P<0.05) .@*Conclusion@#Exposure to cigarette smoke during pregnancy may reduce indicators of offspring ovarian organ index, female rat follicle number and oocyte quality change, the high dose group can lead to oocyte chromatin structure and DNA methylation level anomaly.
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AIM:To investigate molecular regulatory mechanism of K-ras to girdin protein in COS7 cells and expression of K-ras and girdin in colorectal carcinoma tissues .METHODS:The lentiviral vector carrying K-ras gene was constructed and transfected in the COS 7 cells.The expression of K-ras, girdin proteins and other related proteins in COS 7 cells and colorectal carcinoma tissues was observed by Western blot .RESULTS:The COS7 cells with K-ras over-expres-sion showed an irregular cell morphology .The results of Western blot indicated that the downstream signal protein levels of p-ERK1/2, p-Stat3 and girdin were significantly increased in the COS 7 cells with K-ras over-expression.Transfection with the K-ras siRNA into the COS7 cells significantly reduced the protein levels of p-ERK1/2, p-Stat3 and girdin.In the color-ectal carcinoma tissues (7 cases), 5 cases had higher expression of K-ras and girdin compared with pericarcinous tissues . CONCLUSION:K-ras regulates girdin expression through the signal pathway of K-ras-ERK1/2-Stat3-girdin.
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Objective To observe the biological role and the underlying mechanisms of miR-132 in liver cancer on invasion and metastasis.Methods Real-time quantitative polymerase chain reaction (RT-qPCR) analysis was used to examine the expression of miR-132 in four liver cancer cell lines (MHCC97H,HCCLYH,MHCC97L and SMMC-7721),a normal liver cell line HL-7702,and in liver tumor tissues with or without metastases.The biological effects of miR-132 transfection on human liver can-cer cells were assessed by wound assay,matrigel counting and in vivo experiments in nude mice.Western blotting was used to detect the expression of E-cadherin,α-cadherin,vimentin,fibronectin and ZEB2 in li-ver cancer cells.Immunohistochemistry was used to detect positive expression of ZEB2 in xenograft tumors.Results The expressions of miR-132 were downregulated in the four liver cancer cell lines when compared with the normal liver cell line (P ＜ 0.05),and in the liver cancer tissues with distant metastases when compared with the tissues without metastases (P ＜ 0.05).After transfection,ectopic expressions of miR-132 markedly inhibited cell migration and invasion in liver cancer cells.When compared with the control group,the expressions of E-cadherin and α-cadherin in the miR-132 transfection group were significantly increased,but the expressions of vimentin,fibronectin and ZEB2 were decreased.In addition,the numbers of metastatic lung lesions in nude mice in the miR-132 transfection group was markedly decreased when compared with the control group.The expressions of ZEB2 in the miR-132 transfection group was also significantly decreased when compared with the control group.Conclusions Transfection of miR-132 effectively inhibited invasion and metastasis of liver cancer cells in vitro and in vivo.miR-132 may become a new target for regulation of gene expression in liver cancer.
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Objective:Previous studies suggested that the-308G/A allele in the tumor necrosis factor-α(TNF-α) gene promoter (-308G/A) may be a potential risk factor for inflammatory diseases and tumor progression. However, only a few studies have focused on the-308 polymorphism of TNF-αgene with primary lung cancer in Chinese population. This study aims to evaluate the role of TNF-α-308G/A single nucleotide polymorphism (SNP) and the risk of primary lung cancer in Chinese population. Methods:A total of 250 patients and 447 healthy individuals (control group) were involved in this study. Genotyping was performed using TaqMan technology. Results:The frequencies of (GG), (A/G), and (A/G+AA) genotypes of-308G/A SNP in TNF-αgene were 183 (73.2%), 67 (26.8%), and 67 (26.8%) in the patients, and 406 (90.8%), 39 (8.7%), and 41 (9.2%) in the control group, respectively. The distribution of poly-morphism frequencies in the case group and the control group showed a statistically significant difference for the Chinese population (P<0.05). Conclusion:Results indicated that TNF-αgene polymorphism at position-308G/A is associated with susceptibility to lung cancer in Chinese Han population.
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Objective To investigate the epidemiological characterization , effect of prevention and control measures during an outbreak in a military unit caused by Mycoplasma pneumoniae.Methods All the cases were investigated to learn about their basic characteristics , clinical symptoms and aggregation activities using epidemiological cross-sectional study . Results From May 16 to June 11,2013, forty-nine confirmed cases and thirty-five suspected cases who were all males were found at an attack rate of 7.8%.The epidemic peak period was from May 27 to Jun 2(seven days), and the number of total cases was 66(75.9%).During the outbreak, the attack rate of the 10th cadet team, other cadet teams and a non-student population was 47.5%, 4.5% and 1.2% respectively.The difference was significant (P<0.01).The age of forty-nine confirmed cases ranged from 17 to 26 years old , the attack rate did not differ significantly between different age groups, and no aggregation was found in the place of birth and soldier source .The most frequent clinical symptoms were fever and cough for the confirmed cases , 62.5% of whom showed unilateral or bilateral lung inflammation change , while few positive lung symptoms were present .All the confirmed cases were hospitalized and no severe or critically ill cases were present.The outbreak was controlled effectively after implementation of case surveillance , contact precaution , termination of aggregation activities , dispersed habitation and prescription of azithromycin for disease prevention .Conclusion The confined and crowed environment for learning and training can increase the risk of M.pneumoniae outbreak , making it nec-essary to enhance disease prevention awareness , improve case management , live dispersed , reduce close contact and imple-ment personal hygienic measures .
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Recent studies reported that thymoquinone (TQ), a component derived from the medicinal spice Nigella sativa (also called black cumin), exhibited inhibitory effects on cell proliferation of many cancer cell lines. This study was performed to investigate the anti-metastatic effect of thymoquinone on the pancreatic cancer in vitro and in vivo. The results showed that thymoquinone suppressed the migration and invasion of Panc-1 cells in a does-dependent manner. To investigate the possible mechanisms involved in these events, Western blotting analysis was performed, and found that thymoquinone significantly down-regulates NF-kappaB and MMP-9 in Panc-1 cells. In addition, metastatic model simulating human pancreatic cancer was established by orthotropic implantation of histologically intact pancreatic tumor tissue into the pancreatic wall of nude mice. And administration of thymoquinone significantly reduced tumor metastasis compared to untreated control. Furthermore, the expression of NF-kappaB and MMP-9 in tumor tissues was also suppressed after treatment with thymoquinone. Taken together, the results indicate that thymoquinone exerts anti-metastatic activity on pancreatic cancer both in vitro and in vivo, which may be related to down-regulation of NF-kappaB and its regulated molecules such as MMP-9 protein. Consequently, these results provide important insights into thymoquinone as an antimetastatic agent for the treatment of human pancreatic cancer.
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Objective: To investigate the effect of ischemic postconditioning on myocardial infarction and myocardial apoptosis in ischemia-reperfusion injury of rats, and the protective mechanisms thereof. Methods:Thirty-six healthy male Wistar rats(230-280 g) were randomly divided into three groups, ischemia-reperfusion group(Group I-R), ischemia 30 min and reperfusion 120 min without additional intervention; myocardial ischemic postconditioning group(Group Post), after 30 min ischemia, the rats were comprised 3 cycles of 10 seconds reperfusion followed by 10 seconds ischemia, and then the rats were reperfused 120 min; myocardial ischemic postconditioning+AG490(JAK2-STAT3 pathway inhibitor) group(Group Post+AG490), rats were treated with AG490 5 minutes before reperfusion, followed by myocardial ischemic postconditioning and 120 min reperfusion. The myocardial infarct size was measured by TTC staining. Apoptotic index of cardiomyocyte was detected by TUNEL. Results: Myocardial infarct size and myocardium apoptotic index were significantly reduced in Group Post compared to those in Group I-R(P ＜ 0.05). AG490 inhibited cardioprotective effect of ischemic postconditioning. Conclusion: Ischemic postconditioning provides potent cardioprotective effect. JAK2-STAT3 pathway mediates the cardioprotective effects of ischemic postconditioning.
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Objective To discuss how to identify the nerve and prevent the injury of the nonrecurrent laryngeal nerve during thyroid surgery. Methods The clinical data of 3078 patients undergoing thyroid resection were retrospectively analyzed. Results From January 1981 to December 2001,3078 thyroidectomy was performed at our department with the routine exploration of the recurrent laryngeal nerve.4241 recurrent laryngeal nerves were identified,among them there were 12 nonrecurrent laryngeal nerves(0.28%,12/4241),ofwhich all were right-sided.One patient was male and 11 female.Of these 12 cases,there were 2 of type Ⅰ(16.67%,2/12),6 of type Ⅱ(50%,6/12)and 4 of type Ⅲ (33.33%,4/12).One ofthe type Ⅰ patients suffered from intraoperative injury of his nonreurrent laryngeal nerve.Conclusions The careful intraoperative identification of the nonrecurrent laryngeal nerve helps prevent it from the inadvertent injury.