Objective To investigate the correlation between rs712 and rs7973450 located at the 3'UTR region of the KRAS gene and the risk of cervical cancer(CC)and cervical intraepithelial neoplasia(CIN)in Chinese Han population in Yunnan province.Methods A total of 2405 individuals(461 subjects with CIN,961 subjects with CC and 983 healthy controls)were enrolled.The SNPs were genotyped used TaqMan assay and the correlation of these SNPs with CIN and CC was analyzed.Results The A allele of rs7973450 might be a protective factor for the occurrence of CIN(P = 0.004,OR= 0.651,95%CI 0.487～0.871)and CC(P = 7.00×10-4,OR= 0.667,95%CI 0.529～0.844).There was no significant difference in allelic and genotypic distribution of rs712 among CIN,CC and Control groups(P>0.017).The haplotype assay showed thatrs712A-rs7973450G was associated with increased risk of CIN(P = 4.00×10-4;OR= 1.714,95%CI 1.269～2.314)and CC(P = 3.84×10-5,OR= 1.667,95%CI 1.305～2.131).While haplotype rs712A-rs7973450A was associated with a lower risk of CC(P = 0.012,OR= 0.790,95%CI 0.658～0.950).Conclusion The A allele of rs7973450 in 3'UTR of KRAS gene might be the protective factor for the occurrence of CIN and CC in a Chinese Han population in Yunnan province.

OBJECTIVE To investigate the effects and mechanism of luteolin on osteogenic repair of bone defects. METHODS The targets and potential pathways of luteolin in the treatment of bone defects were screened by network pharmacology method， and then the top 2 targets were selected by Hub gene screening for molecular docking verification， with binding energy as the evaluation standard. In vitro experiments were conducted on rat bone mesenchymal stem cells （BMSC） and rat umbilical vein endothelial cells （RUVEC）. Phenotypic validation was performed using alkaline phosphatase staining， alizarin red S staining， and in vitro angiogenesis experiments. Western blot assay was used to detect the protein expressions of phosphatidylinositol 3 kinase （PI3K） and protein kinase 1 （Akt1）， so as to validate the mechanism of luteolin on osteogenic differentiation of BMSC and angiogenesis of RUVEC in vitro. RESULTS The results of network pharmacology showed that the effects of luteolin on vascular formation and bone repair in bone defects were mainly related to Akt1， SRC， estrogen receptor 1， epidermal growth factor receptor， cyclooxygenase 2， matrix metalloproteinase 9 targets， and were closely related to PI3K-Akt signaling pathway. The results of molecular docking showed that luteolin binding to Akt1 and SRC proteins was stable. The results of in vitro experiments showed that luteolin could significantly improve the expressions and activities of alkaline phosphatase in BMSC， increased the number of calcium salt deposits and calcified nodules， and promoted calcification of BMSC. Compared with luteolin 0 μmol/L group， the angiogenesis ability of RUVEC was enhanced significantly in luteolin 1， 10 μmol/L groups， the length of blood vessels and the protein expressions of PI3K and Akt1 were significantly increased （P＜0.05 or P＜0.01）； the higherthe concentration， the better the effect. CONCLUSIONS Luteolin may play a role in promoting angiogenesis and bone repair at the fracture site by activating PI3K/Akt signaling pathway and promoting the protein expressions of PI3K and Akt1.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide. HCC is refractory to many standard cancer treatments and the prognosis is often poor, highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments. Kinesin family member 2C (KIF2C) is reported to be highly expressed in several human tumors. Nevertheless, the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated. In this study, we found that KIF2C expression was significantly upregulated in HCC, and that KIF2C up-regulation was associated with a poor prognosis. Utilizing both gain and loss of function assays, we showed that KIF2C promoted HCC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Additionally, we found that KIF2C is a direct target of the Wnt/β-catenin pathway, and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORC1 signaling. Thus, the results of our study establish a link between Wnt/β-catenin and mTORC1 signaling, which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.
Adult ; Aged ; Animals ; Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition/genetics* ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism* ; Kinesins/metabolism* ; Liver Neoplasms/pathology* ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Neoplasm Staging ; Prognosis ; Protein Binding ; RNA, Small Interfering/metabolism* ; Survival Analysis ; Tumor Burden ; Wnt Signaling Pathway ; Xenograft Model Antitumor Assays ; beta Catenin/metabolism*

Purpose: Non-coding RNA activated by DNA damage (NORAD) has been reported to be a cancer-related long non-coding RNA (lncRNA) implicated in the progression of several cancers; however, its role in breast cancer (BC) has not yet been clarified. Methods: Quantitative real-time polymerase chain reaction was used to examine NORAD, microRNA (miR)-155-5p, and suppressor of cytokine signaling 1 (SOCS1) mRNA expression levels. Western blotting was used to analyze SOCS1 protein expression. The malignancy of BC cells was assessed using the cell counting kit-8 (CCK-8), BrdU, and Transwell assays.Bioinformatics analysis, RNA immunoprecipitation assay, and dual-luciferase reporter gene assays were used to verify the targeted relationship between NORAD and miR-155-5p.Additionally, the regulatory effects of NORAD and miR-155-5p on SOCS1 expression were determined by western blotting. Results: NORAD expression was significantly reduced in BC cell lines and tissues, and its low expression was associated with poor tumor tissue differentiation. NORAD overexpression repressed BC cell proliferation, migration, and invasion, whereas its knockdown produced the opposite effects. Additionally, miR-155-5p was found to be a target of NORAD, and the biological functions of miR-155-5p and NORAD were counteractive. MiR-155-5p was confirmed to target SOCS1, and SOCS1 was found to be positively regulated by NORAD. Conclusion NORAD suppresses miR-155-5p to upregulate SOCS1, thereby repressing the proliferation, migration, and invasion of BC cells.

Purpose: Non-coding RNA activated by DNA damage (NORAD) has been reported to be a cancer-related long non-coding RNA (lncRNA) implicated in the progression of several cancers; however, its role in breast cancer (BC) has not yet been clarified. Methods: Quantitative real-time polymerase chain reaction was used to examine NORAD, microRNA (miR)-155-5p, and suppressor of cytokine signaling 1 (SOCS1) mRNA expression levels. Western blotting was used to analyze SOCS1 protein expression. The malignancy of BC cells was assessed using the cell counting kit-8 (CCK-8), BrdU, and Transwell assays.Bioinformatics analysis, RNA immunoprecipitation assay, and dual-luciferase reporter gene assays were used to verify the targeted relationship between NORAD and miR-155-5p.Additionally, the regulatory effects of NORAD and miR-155-5p on SOCS1 expression were determined by western blotting. Results: NORAD expression was significantly reduced in BC cell lines and tissues, and its low expression was associated with poor tumor tissue differentiation. NORAD overexpression repressed BC cell proliferation, migration, and invasion, whereas its knockdown produced the opposite effects. Additionally, miR-155-5p was found to be a target of NORAD, and the biological functions of miR-155-5p and NORAD were counteractive. MiR-155-5p was confirmed to target SOCS1, and SOCS1 was found to be positively regulated by NORAD. Conclusion NORAD suppresses miR-155-5p to upregulate SOCS1, thereby repressing the proliferation, migration, and invasion of BC cells.

OBJECTIVE：To provide reference for improving the quality sta ndard of Equisetum hyemale . METHODS ：Totally 10 batches of E. hyemale from different sites were collected as samples. TLC method was used to qualitatively identify kaempferol- 3-O-β-sophoroside. The contents of heavy metal ，aflatoxin，impurity，moisture，total ash ，acid-insoluble ash ，water-soluble extract and ethanol-soluble extract were determined according to supplementary provisions of Chinese Pharmacopoeia （2015 edition）. HPLC method was used to determine the content of kaempferol- 3-O-β-sophoroside in sample. HPLC fingerprint of water-soluble extract from E. hyemale was also established. RESULTS ：TLC identification showed that in the chromatogram of the test sample ， fluorescent spots with the same color were displayed on the corresponding positions of the chromatogram of substance control of kaempferol-3-O-β-sophoroside，and without interference from blank control. Among 10 batches of samples ，the contents of impurities were 0.19％-2.32％；the water contents were 10.12％-11.87％；the total ash contents were 6.67％-10.11％；the acid-insoluble ash contents were 1.34％-2.12％；the water-soluble extract contents were 9.17％-13.99％；the ethanol-soluble extract contents were 7.49％-13.68％，respectively. It is preliminarily proposed that the impurity content shall not exceed 3.00％；the total ash content shall not exceed 10.00％；the acid-insoluble ash content shall not exceed 2.50％；the water-soluble extract content shall not be less than 9.00％ ；the ethanol-soluble extract content shall not be less than 5.00％. Arsenic（0.064-0.225 mg/kg） 010815） was detected in 9 batches of samples ；cadmium（0.106-0.132 E-mail：cruise0303@163.com mg/kg）was detected in 6 batches of samples ；lead（0.221- 1.896 mg/kg）was detected in all samples ，but no mercury or rebecca aflatoxin was detected. The results of HPLC method met the relevant requirements of Chinese Pharmacopoeia . The content of kaempferol- 3-O-β-D-sophoroside in 10 batches of samples was 627.12-5 384.53 mg/kg，and the similarity of HPLC fingerprints of 10 batches of samples was more than 0.900. CONCLUSIONS ： A new qualitative and quantitative analysis method for kaempferol- 3-O-β-D-sophoroside was established ；the heavy metals ， aflatoxins，impurities and other items in E. hyemale were detected ；the limits of impurity ，ash and extract were determined. The established method is simple ，accurate and reproducible ，and can be used for quality control of E. hyemale .

Objective: To study the factors affecting the survival and prognosis of patients with intracranial ependymoma. Methods:From January 2008 to January 2018, the prognoses of 276 patients with intracranial ependymoma were analyzed using Log-rank and Cox model analysis. The variables included sex, age, tumor location, tumor diameter, resection extent, pathological grade, Ki-67 index, postoperative radiotherapy, and postoperative chemotherapy. Results: Tumor location, resection extent, and postoperative radiothera-py could all affect the overall survival (OS) and progression-free survival (PFS) of patients with intracranial ependymoma (P<0.001) and independently affected the OS (P<0.001, P<0.001, and P=0.002, respectively) and PFS (P<0.001, P<0.001, and P=0.001, respectively). The Ki-67 index was an independent factor affecting PFS in patients with intracranial ependymoma (P<0.001). The supratentorial loca-tion and Ki-67 index≥10% were independent risk factors indicating poor prognosis (P<0.001). Total resection and postoperative radio-therapy were protective factors (P<0.001 and P=0.001, respectively). Conclusions: Tumor location, resection extent, Ki-67 index, and postoperative radiotherapy are independent factors affecting the prognosis of intracranial ependymoma. It is helpful to extend the PFS and OS of patients through complete tumor resection or postoperative radiotherapy.

BACKGROUND: Cisplatin acquired resistance is a vital problem in the chemotherapy of non-small cell lung cancer, which needs to be further addressed. In recent years, obtaining drug resistant cells from cell cultivation and serving for metabolomics research to find differential metabolites and get potential biomarkers, is a good reference for clinical research and cancer treatment. This study aimed to obtain metabolite information related to cisplatin resistance through metabolomics analysis. METHODS: Metabolites were extracted from A549 cells and cisplatin resistant A549/DDP cells, and ultraperformance liquid chromatography coupled with time of flight mass spectrometry was used to perform metabolomic analysis of endogenous molecules of the two cells and obtain metabolic differences. RESULTS: Through data analysis, 40 metabolites were identified as differential metabolites, mainly involving phospholipids, fatty acids, amino acids and metabolites related to energy metabolism. CONCLUSIONS The drug resistance of A549/DDP cells may be caused by the changes of cell membrane structure and related metabolic pathways.
A549 Cells ; Carcinoma, Non-Small-Cell Lung ; pathology ; Chromatography, High Pressure Liquid ; Drug Resistance, Neoplasm ; Humans ; Lung Neoplasms ; pathology ; Mass Spectrometry ; Metabolomics ; methods

Objective To evaluate the left ventricle systolic function in patients with aortic stenosis (AS) underwent transcatheter aortic valve implantation(TAVI) by speckle tracking imaging and to observe the indicators in bicuspid aortic valves(BAV) and tricuspid aortic valves(TAV) groups.Methods Twenty nine patients with AS were enrolled,all of them underwent TAVI successfully.The regular echocardiography and 3D full-volume images were acquired on before and 3 days,1 month after TAVI.Longitudinal strain,circumferential strain,and three-dimensional left ventricle ejection fraction(3D-LVEF) were analyzed using Qlab software.Results Compared with the baseline,aortic valve blood flow velocity (AV),maximum aortic valve pressure gradient (AVPG-max),mean aortic valve pressure gradient (AVPG-mean),aortic valve area(AVA) after TAVI were improved significantly.Global longitudinal strain(GLS) had a improvement on 3 days after TAVI(all P ＜0.001),and further increased during 1 month after TAVI (all P ＜0.001).Global circumferential strain(GCS) were increased during 1 month after TAVI(all P ＜ 0.001).The 3D-LVEF after 1 month were improved significantly(all P ＜0.001).The BAV patients and TAV patients had similar changes in all of indicators observed.Conclusions The left ventricle systolic function has early improvement after TAVI,and further recovery during follow-up.The BAV patients can obtain a benefit from TAVI equally to the TAV patients.

Objective:To investigate the application of Coronary Artery Disease-Reporting and Data System (CAD-RADS) in the diagnosis of coronary atherosclerotic heart disease(CAD) and its risk factors,and to clarify the effective strength of different risk factors in the diagnosis of CAD by using CAD-RADS.Methods:All the data of 266 patients,who were initially suspected with CAD and underwent CT angiography,were collected and diagnosed by using CAD-RADS and were divided into CAD group(n=174) and non-CAD group(n=69).The informations of age,gender,hypertension,hyperlipemia,diabetes,smoking,serum uric acid (UA) levels,and plasma fibrinogen (FIB) levels of the patients in two groups were analyzed;single factor analysis and multivariate Logstic regression analysis were used to analyze the risk factors of CAD diagnosed by CAD-RADS.Results:Compared with non-CAD group,the ratios of male,hypertension,diabetes,smoking of the patients in CAD group were increased (P<0.05),and the age and the level of UA of the patients in CAD group were also increased (P<0.05).The Logistic regression analysis results showed that age and diabetes were the independent risk factors for CAD diagnosed by CAD-RADS.Conclusion:There are many independent risk factors for CAD diagnosed by CAD-RADS,and age and diabetes are the most correlated risk factors for CAD.