Association between CMTM5 gene and coronary artery disease and the relative mechanism / 北京大学学报(医学版)

OBJECTIVE@#To elucidate the correlation between CKLF-like MARVEL transmembrane domain containing member 5 (CMTM5) gene and the risk of coronary artery disease (CAD), and to detect the effects of CMTM5 gene expression changes on the ability of adhesion and migration of THP-1 cells.@*METHODS@#Using case-control method, a total of 700 hospitalized patients in Shijitan Hospital were enrolled in this study. CAD were diagnosed by coronary angiography, which was defined as at least one blood vessel diameter stenosis ≥50% according to the result of coronary angiography. Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect CMTM5 gene expression; enzyme linked immunosorbent assay (ELISA) method to detect the plasma level of CMTM5; and Logistic regression to analyze CMTM5 genes and the risk of CAD. Human vascular endothelial cells (ECs) and THP-1 cells were cultivated, adhesion and Transwells experiments were used to evaluate the chemotactic capabi-lity of CMTM5 gene on THP-1 cells.@*RESULTS@#In this study, 350 CAD patients matched with 350 control patients were included. RT-PCR results revealed CMTM5 mRNA expression in CAD group was 3.45 times compared with control group, which was significantly higher than that in control group (P < 0.05). The levels of CMTM5 plasma protein in CAD group was (206.1±26.9) μg/L, which was significantly higher than that in control group (125.3±15.2) μg/L (P < 0.05). After adjusted for the risk factors of age, gender, BMI, smoking, hypertension, diabetes and hyperlipidemia, Logistic regression analysis results indicated that CMTM5 was the susceptibility factors of CAD, which still had significant correlation with CAD (P < 0.05). Adhesion and Transwells experiments results revealed that the numbers of adhesion and migration of THP-1 cells in CMTM5 overexpression ECs group (EO group) were significantly higher than that in lenti-mock infected ECs group (EO-MOCK group), non-infected ECs group (EN group), lenti-mock infected ECs group (ES-MOCK group), and CMTM5 suppression ECs group (ES group). On the contrary, the numbers of adhesion and migration of THP-1 cells in ES group were significantly lower than that in the other four groups (P < 0.01).@*CONCLUSION@#CMTM5 gene was closely related to the development of CAD. CMTM5 overexpression promoted the adhesion and migration of THP-1, which might play a part in the mechanisms of atherosclerosis and CAD.

Association of CMTM5 gene expression with the risk of in-stent restenosis in patients with coronary artery disease after drug-eluting stent implantation and the effects and mechanisms of CMTM5 on human vascular endothelial cells / 北京大学学报(医学版)

OBJECTIVE@#To elucidate the correlation between CKLF-like marvel transmembrane domain containing member (CMTM5) gene and the risk of in-stent restenosis (ISR) with coronary artery disease (CAD) patients and to detect the effects and mechanisms of CMTM5-stimulated genes on human vascular endothelial cells (ECs) proliferation and migration.@*METHODS@#A total of 124 hospitalized patients in Shijitan Hospital were enrolled in this study. All the CAD patients were detected with platelet reactivity and grouped into two groups according to platelet reactivity; ISR was conformed by coronary angiography; RT-PCR method was used to detect CMTM5 gene expression; The CMTM5 over expression, reduction and control EC lines were established; Cell count, MTT, Brdu and flow cytometry methods were used to detect the proliferation of ECs, scratch and transwell experiments to test the migration of ECs, Western blot was used to detect signal path expressions.@*RESULTS@#CMTM5 gene expression in HAPR (High on aspirin platelet reactivity) group was 1.72 times compared with No-HAPR group, which was significantly higher than No-HAPR group. HAPR group ISR rate was 25.8% (8 cases), the incidence of No-HAPR ISR group was 9.7% (9 cases), and the results showed that in HAPR group, the incidence of ISR was significantly higher than that in No-HAPR group (P=0.04, OR=0.04, 95%CI=1.16－7.52), which showed that CMTM5 gene was significantly correlated with the risk of ISR. In HAPR group ISR rate was 25.8% (8 cases), the incidence of ISR in No-HAPR group was 9.7% (9 cases), and the results showed that the risk of ISR in HAPR group was significantly higher than that in No-HAPR group. All the results showed that CMTM5 was significantly correlated with the risk of ISR in CAD patients (P < 0.05). CMTM5 overexpression inhibited the proliferation and migration ability of ECs (P < 0.05), PI3K/Akt signaling pathways were involved in the role of regulation on ECs.@*CONCLUSION@#Our results revealed that CMTM5 gene was closely related with ISR, CMTM5 overexpression may repress ECs proliferation and migration through regulating PI3K-Akt signaling.

Association between CMTM5 gene rs723840 single nucleotide polymorphism and coronary artery disease / 解放军医学杂志

Objective To elucidate the correlation between the single nucleotide polymorphism ofCKLF-like MARVEL transmembrane domain containing member 5 (CMTM5) gene rs723840 and the occurrence of coronary artery disease (CAD). Methods The present study is a case-control study. A total of 1110 hospitalized patients in Shijitan Hospital were enrolled in this study. Patients were divided into CAD group (n=560) and control group (n=550). CAD were diagnosed by coronary angiography, which was defined as at least one blood vessel diameter stenosis ≥50% according to the result of coronary angiography. Genotypes were determined by polymerase chain reaction (PCR) and using sequencing analysis to detect rs723840 of CMTM5 gene. The proportions of genotype and allele of CMTM5 gene were analyzed. Results The genotype frequencies in rs723840 C>T of CMTM5 gene conformed well to the Hardy-Weinberg equilibrium in both CAD group and control group. Between the two groups, the genotypes frequency (CC, CT and TT) in CAD and control groups were 53.9%, 40.9%, 5.2% and 69.3%, 28.7%, 2.0%, respectively (P<0.001). T allele frequency was significantly higher than that in C allele frequency (25.6% vs. 16.4%, OR=1.566, 95%CI 1.325-1.850, P<0.001). After adjusted for the risk factors of age, gender, BMI, smoking, hypertension, diabetes and hyperlipidemia, logistic regression analysis results indicated that CMTM5 was the susceptibility factors of CAD, which showed significant correlation with CAD. Conclusions A significant correlation was found between CMTM5 gene rs723840 polymorphism and the occurrence of CAD, T allele carriers are closely related to the occurrence of CAD.

Application of TPGS-based nano-drug delivery system in reversing P-gp mediated multidrug resistance / 药学学报

Multidrug resistance (MDR) seriously affects the clinical efficacy of chemotherapeutic drugs. One of the main mechanisms of MDR is the overexpression of P-glycoprotein (P-gp) in tumor cells that reduces the intracellular drug concentrations and limits the effective use of chemotherapeutic drugs. Accordingly, application of P-gp inhibitors that can reverse tumor MDR is an effective strategy to enhance the anti-tumor effect of chemotherapeutic drugs. In recent years, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) has been widely applied as the potential P-gp inhibitor for its excellent P-gp inhibition effect as well as good safety. In this paper, we reviewed the P-gp inhibitors, the mechanisms of TPGS in reversing P-gp-mediated MDR and the application of TPGS-based nano-drug delivery system.

Treating glioma with umbilical cord mesenchymal stem cells: mechanism of action, safety and future application / 中国组织工程研究

BACKGROUND: Umbilical cord mesenchymal stem cells (UC-MSCs) are a group of cells that have self-renewal, highly proliferative and multidrug differentiation potential. The properties of UC-MSCs and their tumor tropism make them an ideal tool for glioma cell therapy. These cells can act by paracrine or as a delivery system for genes and drugs. It has been demonstrated that UC-MSCs can inhibit the growth of glioma and improve the survival after transplantation into the brain. OBJECTIVE: To summarize the molecular mechanisms and safety of UC-MSCs in the treatment of glioma and to provide a useful reference for further research. METHODS: We searched the PubMed and CNKI databases from 2000 to 2017 with the English terms of "glioma; umbilical cord mesenchymal stem cells" and the Chinese terms of "glioma; umbilical cord mesenchymal stem cells; safety; molecular mechanism". Based on the inclusion and exclusion criteria, 55 articles were finally reserved for review. RESULTS AND CONCLUSION: UC-MSCs have obvious effect on treating glioma. These cells can treat glioma through homing mechanism and paracrine mechanism as gene carrier and co-culture. Moreover, UC-MSCs have certain safety in the treatment of glioma.

A data-driven method for syndrome type identification and classification in traditional Chinese medicine / 中西医结合学报

The efficacy of traditional Chinese medicine (TCM) treatments for Western medicine (WM) diseases relies heavily on the proper classification of patients into TCM syndrome types. The authors developed a data-driven method for solving the classification problem, where syndrome types were identified and quantified based on statistical patterns detected in unlabeled symptom survey data. The new method is a generalization of latent class analysis (LCA), which has been widely applied in WM research to solve a similar problem, i.e., to identify subtypes of a patient population in the absence of a gold standard. A well-known weakness of LCA is that it makes an unrealistically strong independence assumption. The authors relaxed the assumption by first detecting symptom co-occurrence patterns from survey data and used those statistical patterns instead of the symptoms as features for LCA. This new method consists of six steps: data collection, symptom co-occurrence pattern discovery, statistical pattern interpretation, syndrome identification, syndrome type identification and syndrome type classification. A software package called Lantern has been developed to support the application of the method. The method was illustrated using a data set on vascular mild cognitive impairment.

Studies on the correlation of PON1 gene rs854572 single nucleotide polymorphism to clopidogrel resistance / 解放军医学杂志

Objective To investigate the correlation of the single nucleotide polymorphism (SNP) of PON1 (Paraoxonase-1) gene rs854572 to the occurrence of clopidogrel resistance (CR). Methods A case-control method was employed in present study. A total of 850 hospitalized patients with coronary artery diseases (CAD) in General Hospital of Shenyang Command were enrolled. The residual platelet aggregation rate (RPA) induced by 20μmol/L of adenosine diphosphate (ADP) was detected by optical nephelometry, and RPA≥70% was defined as CR. Accordingly, all the enrolled 850 patients were then divided into CR group (n=215) and non-CR (NCR) group (n=635). Polymerase chain reaction (PCR) and pyrophosphate sequencing were executed to determine the genotypes and the allele frequencies of PON1 gene rs854572. Results The genotype frequencies in rs854572 of PON1 gene conformed well to the Hardy-Weinberg equilibrium in both CR group and NCR group. Three frequencies of genotype CC, CG and GG were 23.7%, 49.3%, 27.0% in CR group, and 24.1%, 50.2%, 25.7% in NCR groups, respectively. No significant difference in genotype and allele frequency existed between CR group and NCR group (P=0.93 and 0.76, respectively). Logistic regression analysis revealed that no correlation between rs854572 SNP of PON1 gene and the formation of CR in patients with CAD after adjustment of correspondent factors including age, gender, body mess index, smoking, hypertension, diabetes mellitus and hyperlipidemia. Conclusions It is considered that no correlation exists between PON1 gene rs854572 polymorphism and clopidogrel resistance in patients with coronary heart disease.

Studies on the correlation of PON1 gene rs854572 single nucleotide polymorphism to clopidogrel resistance / 解放军医学杂志

Objective To investigate the correlation of the single nucleotide polymorphism (SNP) of PON1 (Paraoxonase-1) gene rs854572 to the occurrence of clopidogrel resistance (CR). Methods A case-control method was employed in present study. A total of 850 hospitalized patients with coronary artery diseases (CAD) in General Hospital of Shenyang Command were enrolled. The residual platelet aggregation rate (RPA) induced by 20μmol/L of adenosine diphosphate (ADP) was detected by optical nephelometry, and RPA≥70% was defined as CR. Accordingly, all the enrolled 850 patients were then divided into CR group (n=215) and non-CR (NCR) group (n=635). Polymerase chain reaction (PCR) and pyrophosphate sequencing were executed to determine the genotypes and the allele frequencies of PON1 gene rs854572. Results The genotype frequencies in rs854572 of PON1 gene conformed well to the Hardy-Weinberg equilibrium in both CR group and NCR group. Three frequencies of genotype CC, CG and GG were 23.7%, 49.3%, 27.0% in CR group, and 24.1%, 50.2%, 25.7% in NCR groups, respectively. No significant difference in genotype and allele frequency existed between CR group and NCR group (P=0.93 and 0.76, respectively). Logistic regression analysis revealed that no correlation between rs854572 SNP of PON1 gene and the formation of CR in patients with CAD after adjustment of correspondent factors including age, gender, body mess index, smoking, hypertension, diabetes mellitus and hyperlipidemia. Conclusions It is considered that no correlation exists between PON1 gene rs854572 polymorphism and clopidogrel resistance in patients with coronary heart disease.

Study on dosimetry of 125I seed in-plane implantation / 中华核医学杂志

Objective To study the dosimetry of different arrangements of 125I seeds in one plane.Methods Nine different in-plane arrangements of 9 125I seeds (2.035 × 107 Bq/seed) were simulated according to distance (cm) along x (horizontal)- and y( longitudinal )-axis using the 3-dimensional treatment planning system (TPS) (3D-TPS): x0.5, y0. 5; x0. 5, y1.0; x0. 5, y1.5; x1.0, y1.0; x1.0, y1.5;x1.5, y1.5; x0. 5, y0. 5 (2)1.0; x0.5, y1.0 (2)0.5; x1.0, y1.0 (2)0.5. The isodose curves of 40,80, 130, 145 and 200 Gy were created and the area, radius and medical cost under the 40, 80, 130, 145and 200 Gy isodose curves were calculated. Results The area, radius and medical cost under the same isodose curves were significantly different with each 125I seed arrangement. The arrangements which had the biggest area under curves of 40, 80, 130, 145 and 200 Gy isodose were x1. 5, y1. 5; x1. 0, y1. 0; x1. 0,y1. 0; x0. 5, y1. 0 and x0. 5, y1. 0, respectively. Conclusion The matched peripheral dose and therapeutic effect were affected significantly by the geometric arrangement of 125I seeds.

Establishment of a nude mouse model of nasopharyngeal carcinoma lymph node metastasis and screening of the metastasis-related signature genes / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a nude mouse model of nasopharyngeal carcinoma (NPC) lymph node metastasis and screen the signature genes associated with the metastasis.</p><p><b>METHODS</b>The NPC 5-8F-EGFP cells were inoculated into nude mice, from which a 5-8F-LN cell line with lymph node metastasis potential was obtained. The lymphatic metastasis-related signature genes of breast cancer and head and neck squamous cell carcinoma were screened by data mining method.</p><p><b>RESULTS</b>The NPC cell lines 5-8F and 6-10B showed 307 differentially expressed genes by microarray analysis, from which 20 overlapping genes were identified, and 3 overexpressed genes were found with probable metastasis potential, namely the ADM, IRF1, and CAV1 genes. Quantitative RT-PCR validated the data mining results in the 5-8F-EGFP, 6-10B-EGFP, NP69, and 5-8F-LN cell lines. The 3 NPC cell lines 5-8F-EGFP, 6-10B-EGFP and 5-8F-LN showed significantly higher expressions of IRF1 than NP69 cells (P=0.008, 0.022, and 0.006, respectively. The expression level of CAV1 in 5-8F-EGFP cells was significantly higher than that in 6-10B-EGFP cells (P=0.014), but ADM expression showed no significant difference between the 4 cell lines.</p><p><b>CONCLUSIONS</b>IRF1 may play an important role in the progression of NPC. The overexpression of CAV1 in 5-8F-EGFP cells can be associated with the high metastatic potential of the cells.</p>

Refined mapping of the loss of heterozygosity on chromosome 1q21 in gastric carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To obtain allelic loss mapping and define the minimal lost region on chromosome 1q21 in gastric carcinomas, and explore role of 1q21 loss of heterozygosity (LOH) in the development and progression of gastric carcinogenesis.</p><p><b>METHODS</b>Using 7 high-density microsatellite markers and PCR method, lq21 LOH was analyzed in 30 paired specimens of fresh gastric carcinoma, and the relation between 1q21 LOH and the clinicopathological features of the malignancy was tested.</p><p><b>RESULTS</b>The LOH frequency on chromosome 1q21 from these gastric carcinoma tissues reached 60% (18/30). The LOH frequencies of the microsatellite markers D1S514, D1S2696, D1S498, D1S305, D1S2624, D1S2635 and D1S2702 were 13.3%, 10%, 20%, 23.3%, 33.3%, 40% and 23.3%, respectively. The minimal lost region on 1q21 LOH in the gastric carcinoma tissues was located in the region between D1S2624 and D1S2707, in the vicinity of D1S2635. No significant relations of 1q21 LOH to the patients' age, gender, location of the primary foci, clinical staging, or the tumor differentiation were noted (P>0.05), but 1q21 LOH was correlated to lymph node metastases of the malignancy (P<0.05).</p><p><b>CONCLUSION</b>Higher frequency of 1q21 LOH occurs in gastric carcinoma cells, suggesting the presence of potential tumor suppressor genes closely associated with gastric carcinogenesis near the region of D1S2635.</p>

AF172993 sequence of Plunc in GenBank database is not the complete CDS / 南方医科大学学报

<p><b>OBJECTIVE</b>To determine AF172993 sequence is either the complete CDS or a transcript variant.</p><p><b>METHODS</b>RT-PCR was used to amplify the CDS sequence of Plunc, which was subsequently cloned into the pEGFP-N1 eukaryotic expression vector. After bi-directional sequence analysis, the sequence obtained was blasted against the AF172993 sequence, nr database and human genome database.</p><p><b>RESULTS</b>In CDS of the new cloned sequence, the 658 base A in the AF172993 sequence was replaced by C, and the corresponding genetic code was also converted from AAG to CAG, leading to the alteration of the amino acid Gln to Lys. In addition, the base C at the 658 position of the CDS showed perfect match with the base C at 2094188 position in human chromosome 20.</p><p><b>CONCLUSION</b>The base A at the 658 position of AF172993 sequence of Plunc is a mutation site, which alters the coding of the amino acid. AF172993 sequence is actually a transcript variant of Plunc, and the annotation to AF172993 in GenBank database is not correct and need to be revised.</p>

Association of abnormal cyclooxygenase-2 gene expression with colorectal carcinoma metastasis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate cyclooxygenase-2 (COX-2) expression of in colorectal carcinoma cell lines and tissues and its clinical implications.</p><p><b>METHODS</b>SP immunohistochemistry was used to detect COX-2 protein in SW480 and SW620 cell lines and 50 primary colorectal carcinoma and 50 lymphoma metastasis carcinoma specimens. Real-time PCR was used to detect COX-2 mRNA expression in SW480 and SW620 cell lines.</p><p><b>RESULTS</b>SW480 and SW620 cell lines both highly expressed COX-2. The positive expression levels of COX-2 increased significantly in lymph node metastatic carcinoma in comparison with primary colorectal carcinoma (P<0.05). The expression COX-2 mRNA in SW620 cell line was higher than that of SW480 cell line, showing a mean expression increment of 2.268 folds in SW620 cell line relative to SW480.</p><p><b>CONCLUSION</b>Elevated COX-2 expression may be associated with lymph node metastases of colorectal carcinoma.</p>

Exploration of multigene, multistep and multipathway model of nasopharyngeal and colorectal carcinogenesis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To construct tree models for nasopharyngeal carcinoma (NPC)and explore the oncogenesis process of NPC.</p><p><b>METHODS</b>Based on the software which Desper et al developed, tree models were constructed for colorectal carcinoma (CC) from the comparative genomic hybridization (CGH) data of 118 CC patients and for NPC from the CGH data of 140 southern Chinese patients, respectively.</p><p><b>RESULTS</b>Tree models for CC suggested that changes in -18q and +20q were important early events in colorectal carcinogenesis. As changes in -18q occurred prior to those in -17p, there might be some cause-effect relationship. Tree models for NPC suggested that change in -3p was an important early event in nasopharyngeal carcinogenesis, and those in -11q, -14q, -16q, -9p were also non-random genetic events in carcinogenesis, suggesting that there might be tumor-associated genes existing on these chromosome arms. The tree model also suggested the existence of oncogene on the short arm of chromosome 12.</p><p><b>CONCLUSION</b>Constructing tree models based on the CGH data to demonstrate the initiation and progression of NPC might help elucidate its multigene, multistep and multipathway development. It may provide valuable clues to explore the mechanism of tumorigenesis.</p>