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【Objective】 To explore the expression of checkpoint kinase 2 (CHEK2) in clear cell renal cell carcinoma (ccRCC), its association with the clinicopathological features and prognosis, and to predict its relevant molecular signaling pathways and biological functions. 【Methods】 The gene expression data, phenotype data, and corresponding survival information of ccRCC patients were downloaded from TCGA database. The optimal cutoff value of CHEK2 was determined with the "survminer" package. The patients were divided into low and high expression groups, and the association between CHEK2 expression and clinicopathological features was analyzed. The correlation between CHEK2 expression and ccRCC prognosis was evaluated with univariate and multivariate Cox proportional hazard models. The changes of cell signaling pathways involved in different CHEK2 expression levels were explored with gene set variation analysis (GSVA). The correlation between CHEK2 and immune cell infiltration as well as immune checkpoint molecular expression was analyzed. 【Results】 CHEK2 expression was significantly higher in ccRCC tissues than in normal tissues (P<0.01). Higher level of CHEK2 was significantly associated with higher T stage of ccRCC (P<0.01). Kaplan-Meier analysis showed overall survival (OS) of patients with high CHEK2 expression were notably decreased (P<0.001). Univariate and multivariate analyses revealed CHEK2 expression as an independent risk factor of survival (HR=1.950, 95%CI: 1.490-2.570, P<0.001; HR=1.588, 95%CI: 1.185-2.127, P=0.002). GSVA showed that CHEK2 was involved in the following pathways: proximal tubule bicarbonate reclamation, propanoate metabolism, limonene and pinene degradation, fatty acid metabolism, primary immunodeficiency, systemic lupus erythematosus, p53 signaling pathway, homologous recombination, DNA replication and mismatch repair. Correlation analysis suggested that CHEK2 was associated with increased infiltration of multiple immune cells in ccRCC and upregulation of various immune checkpoint molecules. 【Conclusion】 The high level of CHEK2 in ccRCC is an independent predicting factor for poor prognosis. It is probably involved in regulating related events of tumor immune infiltration and may become a new target for ccRCC therapy.
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The aim of this paper is to explore the practical measures of integrating “ideological and political course” into “Psychiatry”. “Ideological and political course” is a key measure to foster character and civic virtue in colleges and universities， and a crucial link of “three -full education”. Based on the characteristics of the course “Psychiatry” and the practical experience of the course “ideological and political work” in the faculty of mental health， North Sichuan Medical College， this paper puts forward the strategies of implementing “ideological and political course” from four aspects： improving teachers’ understanding and practical ability of “ideological and political course”， constructing the integration point of ideological and political course in “Psychiatry”， choosing the teaching methods of “ideological and political course” and evaluating the teaching effect， thus providing references for the implementation of “ideological and political course” in the follow-up professional courses.
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Objective:To investigate the effect of miR-424-5p on radiosensitivity and its mechanism in cervical cancer patients.Methods:The expression levels of miR-424-5p in the cervical cancer tissues and Hela cells were detected by RT-qPCR. The apoptosis rate of Hela cells was determined by flow cytometry. The proliferation activity of Hela cells was detected by CCK-8 assay. The protein expression levels in Hela cells were measured by Western blot.Results:Compared with normal tissues and cells, the expression level of miR-424-5p was significantly down-regulated in the cervical cancer tissues and Hela cells (1.03 vs. 0.88, P<0.01; 1.00 vs. 0.75, P<0.01). Overexpression of miR-424-5p significantly inhibited the proliferation activity of Hela cells after radiation treatment ( P<0.01), and significantly increased the apoptosis rate of Hela cells after radiation treatment (24.82% vs. 49.94%, P<0.001). Overexpression of miR-424-5p inhibited HMGA1 expression (1.01 vs. 0.63, P<0.01). miR-424-5p directly affected HMGA1, thereby impacting the radiosensitivity of cervical cancer radiotherapy. Conclusion:miR-424-5p can improve the radiosensitivity of cervical cancer radiotherapy by directly targeting HMGA1.
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Objective To investigate the clinical utility of magnifying endoscopy combined with nar-row-band imaging( ME-NBI)and endoscopic ultrasonography( EUS)in predicting the depth of early eso-phageal cancer. Methods Sixty-eight patients with early esophageal cancer after gastroscopic and pathological diagnosis were enrolled in Jiangsu Provincal Hospital of Traditional Chinese Medicine from January 2017 to May 2018,ME-NBI and EUS were performed preoperatively to determine the depth of lesion infiltration respectively, the accuracies of the two methods were calculated by referring to the postoperative pathology,and the McNemar test and Kappa test were used for comparison. Results The lesion confined to shallow mucosa and submucosa superficial layer was confirmed in 57 patients by postoperative pathology,submucosa superficial below in 11 pa-tients. Compared with that of histology,the ability of assessment of the invasion depth was moderately consistent with ME-NBI(McNemar test P = 0. 508;Kappa = 0. 560,P < 0. 001),not with EUS(McNemar test P =0. 019;Kappa = 0. 266,P = 0. 015). The accuracy for assessing invasion depth of early esophageal cancer was 86. 8％(59 / 68)by ME-NBI,72. 1％(49 / 68)by EUS,respectively,with statistically significant difference (McNemar test P = 0. 015;Kappa = 0. 258,P = 0. 026). Conclusion ME-NBI and EUS can help to deter-mine the infiltration level of early esophageal cancer. The accuracy of ME-NBI is higher,which is of high value for the formulation of surgical plans for patients.
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Objective To investigate the effect of EZH2 on apoptosis and radiosensitivity of squamous cell carcinoma of tongue.Methods Tongue squamous carcinoma cells Tca-8113 were transfected with small interfering RNA of EZH2 (EZH2 siRNA1,EZH2 siRNA2) and its negative controls (siRNA-NC),the expression levels of EZH2 were detected by RT-PCR and Western blot and EZH2 siRNA2 was used for further studied since its better interference efficiency.The cells with siRNA transfection were irradiated with 8 Gy doses,and cell proliferation was detected by MTT,apoptosis was detected by flow cytometry,the expression of p-STAT3,STAT3 and Cleaved Caspase-3 was detected by Western blot.In addition,the cells were irradiated with 0,2,4,6,and 8 Gy to detect radiosensitivity by cell colony formation assay.Results EZH2 siRNA1 and EZH2 siRNA2 decreased the expression of EZH2 in Tca-8113 cells and EZH2 siRNA2 had a better interference efficiency (tmRNA =8.660,PmRNA ＜ 0.01;tprotein =2.883,Pprotein ＜0.05).The apoptotic rate in the EZH2 siRNA group was (29.90 ± 1.64)％,and was increased by 8 Gy irradiation to (38.17 ± 1.59) ％ (t =4.742,P ＜ 0.05).At the same time,EZH2 siRNA reduced the level of p-STAT3,but promoted the expression of Cleaved Caspase-3 protein,and enhanced the sensitivity of Tca-8113 cells to 1.668-times of control.Conclusions Interfering EZH2 could promote apoptosis,inhibit proliferation and increase radiosensitivity of squamous cell carcinoma of tongue.
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Objective To investigate the effect and mechanism of miR-885-3p on the radiosensitivity of colorectal cancer cell HT-29. Methods The expression of miR-885-3p in HT-29 cells irradiated with different doses (0, 2, 4, 6, 8 Gy) of X-rays was detected by qPCR. The effect of miR-885-3p in modulating cell radiosensitivity was assessed in HT-29 cells with miR-885-3p overexpression. Bioinformatics prediction and dual luciferase reporter gene assay were employed to identify the direct target gene of miR-885-3p. Relationship between miR-885-3p and target gene tyrosine kinase 1 (AKT1) was investigated via regulation of miR-885-3p expression. The effect of AKT1 on radiosensitivity in HT-29 cells was evaluated through knockdown AKT1. The effect of AKT1 on miR-885-3p-induced radiosensitivity was detected by co-transferring miR-885-3p and AKT1 gene into HT-29 cells. Results miR-885-3p expression was up-regulated in radiation-induced HT-29 cells (F=46. 64, P<0. 05). Over-expression of miR-885-3p and knockdown of AKT1 enhanced cell radiosensitization by inhibiting survival and promoting apoptosis (t=12. 33, 12. 95, P <0. 05) with SER of 1. 602 and 1. 946, respectively. Inhibition of miR-885-3p promoted radioresistance by increasing cell survival and inhibiting apoptosis (t=11. 94, P<0. 05) with a SER of 0. 839. AKT1 is a target gene downstream of miR-885-3p, overexpression of AKT1 reversed the effect of miR-885-3p on cell radiosensitivity with a SER of 0. 680. Conclusions miR-885-3p can enhance the radiosensitivity of colorectal cancer HT-29 cells by directly targeting AKT1, which provides a target for improving the radiosensitivity of clinical colorectal cancer.
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Objective To study the protein expression levels of matrix metalloproteinases (MMPs)and their inhibitors in bone tissues of rat femoral head and to explore the relationship between necrosis of femoral head and glucocorticoid.Methods Twenty healthy adult SD rats were randomly divided into glucocorticoid group and control group,with 10 rats in each.Glucocorticoid group was treated with intramuscular injection of hydrocortisone twice a week.The control group received normal saline of the same volume.Four weeks later,bone tissues of left femoral head were collected from each group of rats for HE determination of femoral head necrosis.The expressions of matrix metalloproteinase-1 (MMP-1 ), matrix metalloproteinase-2 (MMP-2 ), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1 ),and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2 )at mRNA and protein levels were detected by RT-PCR and Western blot techniques,respectively.Results The expressions of MMP-1 and MMP-2 at mRNA and protein levels were higher in glucocorticoid group than those in the control group. However,TIMP-1 and TIMP-2 gene and protein expression levels were lower in glucocorticoid group (all P<0.05). Conclusion The expressions of MMPs in bone tissues of rat femoral head in early necrosis were increased,but their inhibitors had decreased expressions. We can draw the conclusion that glucocorticoid-induced necrosis of femoral head may be related to its regulation of the expression levels of MMPs and their related inhibitors.
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AIM:To detect the expression of miRNA-363 and SOX4 in osteosarcoma tissues and to investigate the effect of miRNA-363 on the viability and apoptosis of human osteosarcoma cell line MG-63.METHODS: Real-time PCR was used to detect the expression level and the relationship of miRNA-363 and SOX4 mRNA in the osteosarcoma tis-sues and the corresponding paratumorous tissues collected from 63 patients.The expression levels of miRNA-363 and SOX4 in osteosarcoma cell line MG-63 after transfected with miRNA-363 mimics were measured .The cell viability was measured by CCK-8 assay.Flow cytometry was used to monitor the changes of cell cycle and apoptosis .The changes of SOX4 and miRNA-363 expression levels in the MG-63 cells after transfection with SOX4 siRNA or pcDNA/SOX4 was detect by real-time PCR.RESULTS:The expressed level of miRNA-363 was lower , and the expression level of SOX 4 was higher in the osteosarcoma tissues than those in the adjacent normal tissues .A significantly negative correlation between the expression levels of miRNA-363 and SOX4 was observed .The expression of miRNA-363 in the MG-63 cells after transfection with miRNA-363 mimics was significantly up-regulated, while the expression of SOX4 in the MG-63 cells was significantly down-regulated , with significant difference as compared with the cells transfected with miRNA-NC and control cells .The viability of MG-63 cells was inhibited, the cell cycle was arrested in G0/G1 phase, and the cell apoptosis was increased by transfec-tion with miRNA-363 mimics.The relative protein expression levels of SOX 4 in SOX4 siRNA group and pcNDA/SOX4 group were significantly different from those in negative control group , but the relative expression levels of miRNA-363 had no significant difference .Over-expression of SOX4 restored the viability of the MG-63 cells reduced by miR-363.CON-CLUSION:The expression level of miRNA-363 is low in human osteosarcoma tissue .miRNA-363 may inhibits the viabili-ty of osteosarcoma cell line MG-63 and promotes cell apoptosis in vitro via inhibiting the SOX4 expression.
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A polyimide coated stir bar for sorptive extraction (SBSE) was prepared by immersion precipitation method, and evaluated by using 5 phenols and chlorinated phenols as model samples. The extraction efficiency of the prepared stir bar was the highest compared with commercial extraction phases of SBSE. Experimental parameters including stir speed, ionic strength, extraction temperature, extraction time, desorption temperature and time were optimized. Under the optimal conditions such as 100 mL of sample, 30 g of NaCl, extraction time of 30 min, stirring speed of 800 r/ min and at 25℃, the target compounds were recovered by thermal desorption at 300℃ for 4 min, more than two orders of magnitude of linearity was obtained (R≥0. 9995), LOQs (S/ N=10) were 0. 028-0. 123 μg/ L, and RSDs were in the range of 1. 6% -9. 7% . The polyimide SBSE coupled with gas chromatography-mass spectrometry was applied to the extraction/ enrichment and analysis of phenols in real samples, including tap water, sea water, and waste water. It was found that the polyimide SBSE showed high selectivity towards polar compounds and high thermostability up to 350℃.
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<p><b>BACKGROUND</b>Von Hippel-Lindau (VHL) disease is a hereditary tumor disorder caused by mutations or deletions of the VHL gene. Few studies have documented the clinical phenotype and genetic basis of the occurrence of VHL disease in China. This study armed to present clinical and genetic analyses of VHL within a five-generation VHL family from Northwestern China, and summarize the VHL mutations and clinical characteristics of Chinese families with VHL according to previous studies.</p><p><b>METHODS</b>An epidemiological investigation of family members was done to collect the general information. A retrospective study of clinical VHL cases was launched to collect the relative clinical data. Genetic linkage and haplotype analysis were used to make sure the linkage of VHL to disease in this family. The VHL gene screening was performed by directly analyzing DNA sequence output. At last, we summarized the VHL gene mutation in China by the literature review.</p><p><b>RESULTS</b>A five-generation North-western Chinese family afflicted with VHL disease was traced in this research. The family consisted of 38 living family members, of whom nine were affected. The individuals afflicted with VHL exhibited multi-organ tumors that included pheochromocytomas (8), central nervous system hemangioblastomas (3), pancreatic endocrine tumors (2), pancreatic cysts (3), renal cysts (4), and paragangliomas (2). A linkage analysis resulted in a high maximal LOD score of 8.26 (theta = 0.0) for the marker D3S1263, which is in the same chromosome region as VHL. Sequence analysis resulted in the identification of a functional C>T transition mutation (c. 499 C>T, p.R167W) located in exon 3 of the 167 th codon of VHL. All affected individuals shared this mutation, whereas the unaffected family members and an additional 100 unrelated healthy individuals did not. To date, 49 mutations have been associated with this disease in Chinese populations. The most frequent VHL mutations in China are p.S65 W, p.N78 S, p.R161Q and p.R167 W.</p><p><b>CONCLUSIONS</b>The results supported the notion that the genomic sequence that corresponds to the 167 th residue of VHL is a mutational hotspot. Further research is needed to clarify the molecular role of VHL in the development of organ-specific tumors.</p>
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Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Asian People , China , Haplotypes , Genetics , Mutation , Pedigree , Retrospective Studies , Von Hippel-Lindau Tumor Suppressor Protein , Genetics , von Hippel-Lindau Disease , Diagnosis , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To downregulate the expression of pituitary tumor transforming gene 1 (PTTG1) in osteosarcoma (OS) cells by siRNA technology and to investigate related biological impact on cell proliferation, cell cycle and cell invasion of OS.</p><p><b>METHODS</b>Three OS cell lines and osteoblast hFOB1.19 cell line were used in this study. Control siRNA and PTTG1 siRNA were employed to transfect OS U2OS cells, and PTTG1 protein level was detected by Western blot after the transfection. Effects of PTTG1 siRNA on cell proliferation, cell cycle and cell invasion were investigated by CCK-8, flow cytometry and Boyden chamber, respectively. Finally, activity of Akt and its downstream target gene expression were analyzed by Western blot in U2OS cells upon various treatments.</p><p><b>RESULTS</b>Expression of PTTG1 protein in 3 OS cells (MG-63, SaOS-2 and U2OS) was significantly higher than that in osteoblast hFOB1.19, among which U2OS cells displayed the highest level. PTTG1 siRNA markedly downregulated the expression of PTTG1 protein in U2OS cells, leading to obvious inhibition of cell proliferation, altered cell cycle distribution and reduced ability of invasion of U2OS cells. Moreover, downregulation of PTTG1 reduced the expression of p-Akt (S473 and T308), MMP-2 and MMP-9 proteins, along with enhanced expression of p21 and E-cadherin proteins.</p><p><b>CONCLUSIONS</b>PTTG1 may be tightly linked to the development of OS and therefore may serve as a novel target for precision therapy of OS.</p>
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Humans , Bone Neoplasms , Metabolism , Pathology , Cadherins , Metabolism , Cell Cycle , Physiology , Cell Movement , Cell Proliferation , Physiology , Down-Regulation , Matrix Metalloproteinase 2 , Metabolism , Matrix Metalloproteinase 9 , Metabolism , Neoplasm Invasiveness , Osteosarcoma , Metabolism , Pathology , RNA, Small Interfering , Pharmacology , Securin , Genetics , Metabolism , TransfectionABSTRACT
Objective To investigate the radiation dose levels to the adults examined from diagnostic exposure in Beijing. Methods The radiation doses to the examined individuals were measured by using individual diagnostic radiology equipments in 30 random hospitals from a total of 10 districts and suburban areas, including 1 182 samples of X-ray photography,542 samples of mammography and 410 samples of CT examination. Results 2 134 samples were measured in this study. The dose ranges of X-ray photography, CR, and DR were 0?4 -24?1, 0?3 -13?9 and 0?1 -15?9 mGy, respectively. The average dose range of glandular breast was 0?3-5?4 mGy. In 410 CT samples the value of CTDIw , CTDIvol and DLP were 28?1 - 96?3 mGy, 7?0 - 23?4 mGy, and 162?2 - 898?1 mGy·cm, respectively. Conclusions Several dose levels from diagnostic examination were higher than guidance level for medical exposure in GB 18871-2002,which should be noted.
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Objective To assess the clinical factors impacting on the effective time of endocrine therapy for patients with prostate cancer.Methods The chnical data of 432 patients with prostate cancer who accepted endocrine therapy were analyzed retrospectively.The endpoint of the study was failure of endocrine therapy which was defined as continuous elevation of prostate specific antigen (PSA) from nadir for 2 times and more than 0.2 μg/L.The clinical data such as age,clinical stage,lymph node metastasis,bone metastasis,Gleason score,initial PSA,and PSA nadir were collected and their rehtionship with the effective time of endocrine therapy were further assessed via COX regression model.Results Age of onset was 57-88(73.70 ± 7.28) years.Initial PSA was 10.30-588.10(27.15 ± 75.90) μ g/L.The effective time of endocrine therapy was 3-62 (27.01 ± 13.10) months.Univariate regression analysis showed that initial PSA,clinical stage,Gleason score,PSA nadir,lymph node metastasis,bone metastasis were correlated with the effective time of endocrine therapy (P ＜ 0.01).Multivariate regression analysis showed that only Gleason score was correlated with the effective time of endocrine therapy(P=0.001).Compared with patients with Gleason score equal to or less than 3+4,patients with Gleason score equal to or more than 4+3 showed 2.49 fold increased risk of therapy failure (OR =2.49,95％ CI 1.44-4.30).Conclusion Gleason score has close relationship with the effective time of endocrine therapy for patients with prostate cancer,Gleason score equal to or more than 4+3 is an indicator for poor response to endocrine therapy.
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Objective To monitor the levels of radioactive contamination due to the Japanese Fukushima nuclear accident in Beijing,so as to provide scientific technical information for government to draw effective controlling strategy and processing mechanism.Methods The system of nuclear emergency nmonitoring was started,then the radioactive contamination levels of atmosphere,rain water,surface water and vegetables in Beijing were detected according to the relative survey regulations and technology criterions.Results During the period from 15 to 41 d after the accident,obvious radioactive contamination was found in the atmosphere of Beijing.The maximum radioactivity concentration of 131I ( 5.89 mBq/m3 ) was detected at 22 d after the accident.The radioactivity concentrations of 137Cs and 134Cs were surveyed forming their corresponding peaks at 20 d after the accident,but they were one magnitude lower than the peak value of 131I at least.In addition,the gross β radioactivity level in the water of Chao Bai-he river was verified to be in the range of 0.314 - 0.602 Bq/L. Conclusions The radioactive contamination due to Fukushima nuclear accident has not done visible harm to the public health in Beijing,but monitoring should be continued to observe the long-term effect of the accident.
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To investigate the disposition and tissue distribution of ML12 after intravenous (iv) administration in rats, the compound in plasma or in tissue was extracted into ethyl acetate under basic condition and was determined by HPLC after extracted by dilute sulfuric acid. Excitation wavelength and emission wavelength of fluorescence detection were 278 nm and 307 nm, respectively. The data were processed with the software 3P97 to calculate the main pharmaceutical parameters of ML12. At dose of 5 and 10 mg/kg, the elimination of the drug from plasma was found to be kinetically linear, but when the dosage was 20 mg/kg, a non-linear feature was observed. The highest level of ML12 was found in the kidney. Distribution of ML12 after iv administration was extensive and the concentration-time profile was found to be fitted to an open two-compartment model.