Driver gene mutations among non-small cell lung cancer tissues and its clinical significance / 临床与实验病理学杂志

Purpose To investigate the mutation rate of EGFR,KRAS,ALK and ROS1 in non-small cell lung cancer (NSCLC) and its association with clinical or pathological characteristics.Methods 86 NSCLC tissues were included.Fluorescence PCR was used to detect the EGFR,KRAS mutation and ALK,ROS1 fusion gene.The association between EGFR,KRAS,ALK and ROS1 gene and age,gender,smoking history,histological type,lymph node metastasis and other clinical pathological features were analyzed.Results The total mutation rate of the driver gene in NSCLC patients was 62.8％ (54/86).EGFR mutation rate was 76％ (41/54).KRAS mutation rate was 9.3％ (5/54).ALK gene fusion mutation rate was 13.0％ (7/54),and in one of the patients,EGFR 19 deletion mutation and ALK fusion co-exist.ROS1 gene fusion mutation was 3.8％ (2/54).EGFR gene mutation rate was higher in adenocarcinoma and female (P ＜ 0.05),but no significant association was found in age,smoking history and lymph node metastasis (P ＞0.05).KRAS,ALK,ROS1 genes had no obvious correlation with clinical pathological features (P ＞ 0.05).Conclusion The EGFR mutation and ALK fusion was rather high in patients with NSCLC.More attention should be paid to them.Though KRAS,ROS1 mutations and double mutations were low in NSCLC patients,they should not be ignored.

Expression profile of miR-501-5p in lung adenocarcinoma patients from Xuanwei area / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relationship between miR-501-5p expression and the clinicopathological factors in patients with lung adenocarcinoma in Xuanwei area.</p><p><b>METHODS</b>Surgical specimens of lung adenocarcinoma and paired adjacent tissues from 24 patients with lung adenocarcinoma from Xuanwei area were examined for miR-501-5p expression using microRNA microarray technique and qPCR. Chi-square test was used to analyze the association of miR-501-5P expression with the clinicopathological characteristics of the patients. Multiple regression analysis was performed to analyze the association of miR-501-5p expression with the patients' gender, age, tumor stage, and preoperative CEA level.</p><p><b>RESULTS</b>MicroRNA microarray analysis and qPCR validation results revealed significantly upregulated expressions of miR-501-5p in patients with lung adenocarcinoma from Xuanwei area (Plt;0.01). The microarray data showed an up-regulation of miR-501-5p by 3.17 folds in lung adenocarcinoma tissue compared with the adjacent tissue (P=0.22376, FDR=0.071395). Chi-square test indicated that miR-501-5p expression level was associated with the patients' age (f=7.168, P=0.014), TNM stage (f=36.627, P<0.01), and preoperative serum CEA level (f=30.045, Plt;0.01), but not with the patients' gender (f=3.612, P=0.071). Multiple regression analysis revealed that miR-501-5p expression was positively correlated with the patients' age, TNM stage of the tumor, and serum CEA (Plt;0.05).</p><p><b>CONCLUSION</b>miR-501-5p expression is up-regulated in lung adenocarcinoma with significant associations with the patients' age, TNM stages and serum CEA level in patients from Xuanwei area, suggesting its potential role in the tumorigenesis and progression of lung adenocarcinoma in Xuanwei area.</p>

Anti-fibrotic effects of Salvia miltiorrhiza and Ligustrazine Injection on LX-2 cells involved with increased N-myc downstream-regulated gene 2 expression / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Salvia miltiorrhiza and Ligustrazine Injection (SML) on proliferation and apoptosis of human hepatic stellate cell LX-2 and the expression of N-myc downstreamregulated gene 2 (NDRG2, a tumor suppressor gene).</p><p><b>METHODS</b>HSCs from the LX-2 cell line were cultured in vitro. The proliferative state of different initial LX-2 cell numbers was measured using a 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. LX-2 cells were plated in 96-well plates at an approximate density of 2.50×10cells/mL and cultured for 24 h followed by the application of different concentrations of SML (1, 2, 4 and 8 μL/mL). Cell proliferation was measured using the MTT assay at 24 and 48 h. Apoptosis was detected by flow cytometry at 24 h. LX-2 cells were treated with different concentrations of SML and extracted with protein lysis buffer. The levels of NDRG2 and β-catenin were measured by Western blot.</p><p><b>RESULTS</b>With the exception of the 1 and 2 μL/mL concentrations, 4 and 8 μL/mL SML inhibited cell proliferation in a concentration-dependent manner at 24 and 48 h (P<0.05). With the exception of the 1 and 2 μL/mL concentrations, the NDRG2 expression level was greatly increased in a concentration-dependent manner. However, the level of β-catenin was unaffected.</p><p><b>CONCLUSION</b>SML inhibit LX-2 cell proliferation in a concentration-dependent manner, and the mechanism may be associated with NDRG2 over-expression.</p>

Specific microRNA expression profiles of lung adenocarcinoma in Xuanwei region and bioinformatic analysis for predicting their target genes and related signaling pathways / 南方医科大学学报

<p><b>OBJECTIVE</b>To identify differentially expressed microRNAs (miRNAs) related to lung adenocarcinoma in Xuanwei region and predict their target genes and related signaling pathways based on bioinformatic analysis.</p><p><b>METHODS</b>High-throughput microarray assay was performed to detect miRNA expression profiles in 34 paired human lung adenocarcinoma and adjacent normal tissues (including 24 cases in Xuanwei region and 10 in other regions). Gene ontology and KEGG pathway analyses were used to predict the target genes and the regulatory signaling pathways.</p><p><b>RESULTS</b>Thirty-four miRNAs were differentially expressed in lung adenocarcinoma tissues in cases in Xuanwei region as compared with cases in other regions, including 23 upregulated and 11 downregulated miRNAs. The predicted target genes included GF, RTK, SOS, IRS1, BCAP, CYTOKINSR, ECM, ITGB, FAK and Gbeta;Y involving the PI3K/Alt, WNT and MAPK pathways.</p><p><b>CONCLUSION</b>The specific microRNA expression profiles of lung adenocarcinoma in cases found in Xuanwei region allow for a better understanding of the pathogenesis of lung adenocarcinoma in Xuanwei. The predicted target genes may involve the PI3K/Alt, WNT and MAPK pathways.</p>

Expression of transcription factor SOX4 and its clinical significance in female lung cancer patients in Xuanwei area, Yunnan Province / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of transcription factor SOX4 in lung cancer tissues of female patients in Xuanwei area, Yunnan Province, and explore its correlation with clinicopathological characteristics and prognosis of the female patients.</p><p><b>METHODS</b>Real-time PCR was applied on lung cancer specimens and their corresponding normal lung tissues from 96 female cases of Xuanwei area to assess the expression of SOX4 mRNA. Immunohistochemical staining was performed to investigate the SOX4 protein expression, and further to elucidate its correlation with clinicopathological characteristics and prognosis.</p><p><b>RESULTS</b>The expression level of SOX4 mRNA in the cancer tissues (2.53 ± 1.65) was significantly higher than that of matched normal tissues (1.43 ± 1.14, P = 0.003). Immunohistochemical staining showed that there were 53.1% (51/96) positive expression of SOX4 protein in the cancer tissue and only 26.0% (25/96) in matched normal tissue (P < 0.001). The expression of SOX4 protein had a significant correlation with clinical stage, lymph node metastasis and differentiation of tumor (P < 0.05). The survival analysis by Kaplan-Meier method showed that patients with positive expression of SOX4 protein, lymph node metastasis and advanced tumor stage had a significantly shorter median survival time (P < 0.05). Cox regression survival analysis showed that pathological grade was a significant independent factor affecting prognosis.</p><p><b>CONCLUSIONS</b>The expressions of SOX4 mRNA and protein are significantly up-regulated in Xuanwei female lung cancer patients. Patients with positive SOX4 expression have a shorter median survival time. SOX4 protein expression level combined with pathological grade can be used as a prognostic indicator of female lung cancer patients in Xuanwei area, Yunnan Province.</p>

Detrimental effect of electromagnetic pulse exposure on permeability of in vitro blood-brain-barrier model / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the effect of electromagnetic pulse (EMP) exposure on permeability of in vitro blood-brain-barrier (BBB) model.</p><p><b>METHODS</b>An in vitro BBB model, established by co-culturing brain microvascular endothelial cells (BMVEC) and astroglial cells (AC) isolated from rat brain, was exposed to EMP at 100 kV/m and 400 kV/m, respectively. Permeability of the model was assayed by measuring the transendothelial electrical resistance (TEER) and the horseradish peroxidase (HRP) transmission at different time points. Levels of BBB tight junction-related proteins were measured at 0, 1, 2, 4, 8, 12, 16, 20, 24 h after EMP exposure by Western blotting.</p><p><b>RESULTS</b>The TEER level was lower in BBB model group than in control group at 12 h after EMP, exposure which returned to its normal level at 24 h. The 24 h recovery process was triphasic and biphasic respectively after EMP exposure at 100 kV/m and 400 kV/m. Following exposure to 400 kV/m EMP, the HRP permeability increased at 1-12 h and returned to its normal level at 24 h. Western blotting showed that the claudin-5 and ZO-1 protein levels were changed after EMP exposure.</p><p><b>CONCLUSION</b>EMP exposure at 100 kV/m and 400 kV/m can increase the permeability of in vitro BBB model and BBB tight junction-related proteins such as ZO-1 and claudin-5 may change EMP-induced BBB permeability.</p>

The pathological changes and apoptosis of spleen lymphocytes in mice induced by electromagnetic pulses / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the effects of electromagnetic pulses (EMP) on pathological changes and apoptosis of spleen lymphocytes in mice.</p><p><b>METHODS</b>The male BALB/c mice (18 ∼ 22 g) were sham-exposed or exposed to EMP at 200 kV/m for 400 pulses a day for 7 days. On the 1st, 3rd, 7th, 14th 28th days after exposure the mice were killed. The weight of mice, the pathological change and the weight of mouse spleens were observed, the spleen indexes were calculated. The lymphocytes extracted from spleens were counted. The apoptosis and cell cycle of the lymphocyte were detected by flow cytometry, and the migration of the lymphocyte was measured by transwell assay.</p><p><b>RESULTS</b>No pathological changes were found on the first day after exposure. However, the expanded sinusoid and the changed structure of spleen corpuscle on the 3rd day after exposure were observed. There was no difference of spleen indexes between the sham group and the exposure group on the 1st and 14th day after exposure. On the 3rd and 7th days after exposure, the spleen indexes of exposure group were significantly higher than those of sham-exposure group (P < 0.05). On the 28th day after exposure, the spleen indexes of exposure group was significantly lower than those of sham-exposure group (P < 0.05). The number of spleen lymphocytes on the 3rd and 7th days after exposure in exposure group increased significantly, compared with sham-exposure group (P < 0.05). But there were no differences of apoptotic cells and cellular cycle between the exposure group and sham-exposure group (P > 0.05). The ability of migration of the exposure group was significantly higher than that of sham-exposure group (P < 0.05). than the sham group (P < 0.05).</p><p><b>CONCLUSION</b>The spleen of the male mouse is one of the target organs of EMP. After exposure to EMP, the number of spleen lymphocytes increased. But there were no differences of cell apoptotic cells and cell cycle between the sham group and the exposure group, due to the enhanced migration of lymphocytes induced by EMP.</p>

Effect of electromagnetic pulse exposure on brain micro vascular permeability in rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To observe the effect of electromagnetic pulse (EMP) exposure on cerebral micro vascular permeability in rats.</p><p><b>METHODS</b>The whole-body of male Sprague-Dawley rats were exposed or sham exposed to 200 pulses or 400 pulses (1 Hz) of EMP at 200 kV/m. At 0.5, 1, 3, 6, and 12 h after EMP exposure, the permeability of cerebral micro vascular was detected by transmission electron microscopy and immunohistochemistry using lanthanum nitrate and endogenous albumin as vascular tracers, respectively.</p><p><b>RESULTS</b>The lanthanum nitrate tracer was limited to the micro vascular lumen with no lanthanum nitrate or albumin tracer extravasation in control rat brain. After EMP exposure, the lanthanum nitrate ions reached the tight junction, basal lamina and pericapillary tissue. Similarly, the albumin immunopositive staining was identified in pericapillary tissue. The changes in brain micro vascular permeability were transient, the leakage of micro vascular vessels appeared at 1 h, and reached its peak at 3 h, and nearly recovered at 12 h, after EMP exposure. In addition, the leakage of micro vascular was more obvious after exposure of EMP at 400 pulses than after exposure of EMP at 200 pulses.</p><p><b>CONCLUSION</b>Exposure to 200 and 400 pulses (1 Hz) of EMP at 200 kV/m can increase cerebral micro vascular permeability in rats, which is recoverable.</p>