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Objective:To detect the mRNA expression and methylation status of leucine rich repeat containing 55(LRRC55) gene in pancreatic carcinoma tissues, and discuss the clinical value.Methods:Resected pancreatic ductal adenocarcinoma and normal adjacent specimens from 37 patients admitted in General Surgery of First Affiliated Hospital of Naval Medical University were collected from May 2019 to May 2021. Another two normal pancreas specimens and two blood samples from healthy adults were also collected. All patients′ age, gender, tumor location, tumor size, tumor differentiation, TNM staging, lymphatic metastasis, CEA and CA19-9 level were recorded. Bisulfite treatment of genomic DNA and sequencing analysis was used to study methylation patterns in CpG islands of the promoter for LRRC55 gene in fresh tissues from 2 pancreatic adenocarcinoma and adjacent tissues, 2 normal pancreatic tissues, 2 pancreatic cancer cell lines (PaTu8988 and ASPC1). LRRC55 mRNA in 35 pancreatic adenocarcinoma and adjacent tissues was detected by real-time quantitative PCR and the correlations with clinical parameters were analyzed.Results:CpG islands of LRRC55 in pancreatic adenocarcinoma tissues and pancreatic cancer cell lines was highly methylated and the mean methylation rate was 53% and 71%, respectively; while LRRC55 gene in pancreatic adjacent tissues and normal pancreatic tissues was lowly methylated, and the mean methylation rate was 8% and 11%. The relative expression in the pancreatic adenocarcinoma tissues and the paired adjacent normal tissues was 0.21 (0.02, 1.00 ) and 0.98 (0.33, 3.66 ), respectively; the former was significantly lower than the later and the difference was statistically significant ( P=0.003). Correlation analysis showed that LRRC55 mRNA expression level was related to tumor differentiation and CEA, but not correlated with patients′ age, gender, tumor location and size, CA19-9 level, lymphatic metastasis and TNM staging. Conclusions:Pancreatic cancer tissue and cell lines had abnormal methylation of LRRC55 gene; LRRC55 gene hypermethylation was related with its lower mRNA expression level in pancreatic cancer, which was correlated with the tumor differentiation and CEA level. LRRC55 may be a potential suppressor gene for pancreatic cancer.
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OBJECTIVE：To study the intervention effects of Huan gqi injecti on on leucopenia model mice. METHODS ： Kunming mice were randomly divided into normal group ，model group and drug group ，with 8 mice in each group. Model group and drug group were given intraperitoneal injection of cyclophosphamide to induce leukopenia model. Normal group was given intraperitoneal injection of equal volume of sterile water. After modeling successfully ，normal group and model group were given intraperitoneal injection of equal volume of sterile water ；drug group was given intraperitoneal injection of Huangqi injection 0.04 mL/10 g，once a day ，for consecutive 7 d. Based on the detection of blood routine indexes （leukocyte，lymphocyte，neutrophil， monocyte count ）of mice in each group ，the metabolites in serum were analyzed by LC-MS. Principal component analysis （PCA）， partial least squares discriminant analysis （PLS-DA），orthogonal partial least squares-discriminant analysis （OPLS-DA），HMDB， METLIN， KEGG and other databases as well as related literatures were used to identify the differential metabolites. The metabolic pathways of differential metabolites were analyzed with MetPA online tools ，and the correlation of blood routine indexes and differential metabolites were analyzed on the basis of Pearson correlation coefficient. RESULTS： Compared with normal group ， blood rountine indexes of model group were decreased significantly （P＜ 0.01）. Compared with model group ，above blood r ountine indexes of drug group were all increased siginificantly （P＜0.01）. LC-MS chromatogram of serum samples in normal group and model group were significantly different ，and LC-MS metabonomics data of serum samples in drug group were similar to those of normal group. Multivariate statistical analysis and correlated database analysis revealed that compared with normal group ，serum contents of 17 metabolites as L-isoleucine，eicosapentaenoic acid were increased significantly in model group ，while the contents of 4 metabolites as spermidine were decreased significantly （P＜0.05 or P＜0.01）. Compared with model group ，Huangqi injection could reverse the serum contents of 9 metabolites in mice ，such as citric acid ，L-proline，acetylcarnitine，L-isoleucine， L-phenylalanine，sphingosine-1-phosphate，lysophosphatidylinositol，eicosapentaenoic acid and linoleic acid （P＜0.05 or P＜ 0.01），which were associated with linoleic acid metabolism ，biosynthesis of phenylalanine ，tyrosine and tryptophan ，and phenylalanine metabolism （metabolism pathway influential values were all higher than 0.1）. Correlation analysis showed that there was a significant correlation between blood routine indexes and the contents of D-sphingosine，linoleic acid and citric acid in model group（the absolute values of r were generally greater than 0.5）. CONCLUSIONS ：Huangqi injection can increase the counts of leukocytes，lymphocytes，neutrophils and monocytes in leucopenia model mice. The increase of leukocytes may be related to linoleic acid metabolism ，biosynthesis of phenylalanine ，tyrosine and tryptophan ，and phenylalanine metabolism.
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@#Conformational restriction has become one of the important strategies for modification and optimization of lead compounds in structure-based drug design. In this review, we select some recent practical examples from literature to present applications of conformational restriction in structure-based drug design. By introducing fused rings, macrocycles, spiral rings, cyclopropyl groups, bridging rings, methyl groups into molecules, we can find that the conformational restriction strategy is widely used in improving pharmacokinetic properties, enhancing the activity and selectivity, and increasing the novelty of compounds. By using these conformational restriction strategies, the drug-like properties of lead compounds can be significantly improved. This paper can help to provide theoretical guidance and practical experience for innovation in drug design and development.
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Objective To evaluate the effect of problem-based learning (PBL)versus tradi-tional methods in medical statistics. Methods Computer retrieval was conducted to search for con-trolled studies comparing PBL and traditional methods. The quality of included studies was critically evaluated and data were analyzed by using the Cochrane Collaboration's RevMan 5.0 software. Results A total of 21 articles were retrieved,but only 7 were included. The results of Meta analysis showed that there was no significant difference between PBL and traditional methods in both the passing rate of student's score (RR=1.09,95%CI=0.98-1.23,P=0.12>0.05)and the exact score (WMD=0.30, 95%CI=-0.06 -0.67,P=0.10>0.05). Conclusion PBL showed no better learning results in medical statistics compared with traditional methods.
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The occurrence and development of malignant glioma are closely related to abnormal overexpression and activation of receptor tyrosine kinase (RTK) signal transduction pathways.Targeted therapeutic drugs such as RTK inhibitors,RTK downstream signaling pathway inhibitors and multi-target inhibitors can targeting treat malignant glioma at molecular level,some of which have been investigated in clinical trials and achieved good therapeutic effects.
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ObjectiveTo assess the current situation of postgraduates knowledge about medical research design and optimize the curriculum setting of research design.MethodsAn investigation was carried out in the postgraduates of 2011 using questionnaires in a medical university..The questionnaire ineluded basic information of participants and cognition of basic methods of research design.ResultsA total of 473 postgraduates participated in the investigation.Among them,311 systematically learned medical statistics before enrollment,and 275 ( 58.14％ ) once participated in scientific researches.Most of them ( ＞80％ ) knew about the 10 basic methods of research design listed in the questionnaire,but only a few of them were familiar with them,and some even didn't know about the methods.ConclusionWe should pay attention to the culture of scientific research thought in statistical design,strengthen the practice of research design teaching,and the curriculum of research design should be led into undergraduate course.