Convergent evidence has been collected to support that Alzheimer's disease (AD) is associated with reduction in hippocampal volume based on anatomical magnetic resonance imaging (MRI) and impaired functional connectivity based on functional MRI. Radiomics texture analysis has been previously successfully used to identify MRI biomarkers of several diseases, including AD, mild cognitive impairment and multiple sclerosis. In this study, our goal was to determine if MRI hippocampal textures, including the intensity, shape, texture and wavelet features, could be served as an MRI biomarker of AD. For this purpose, the texture marker was trained and evaluated from MRI data of 48 AD and 39 normal samples. The result highlights the presence of hippocampal texture abnormalities in AD, and the possibility that texture may serve as a neuroimaging biomarker for AD.
Abstract Background: Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully understood. Methods: We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells. In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin. Results: Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxia-telangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin sensitivity. Conclusion: In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.
Astrocyte plays important roles in the pathogenesis of ischemic stroke and reperfusion injury. They intensively participate in the energy metabolism of the brain, while their heterogeneity and function after ischemic stroke remain controversial. By employing single-cell sequencing of mice cortex at 12 h after transient middle cerebral artery occlusion (tMCAO) and comparing with the similar published datasets of 24h after tMCAO, we uncover the cellular phenotypes and dynamic change of astrocytes at the acute phase of ischemic stroke. In this study, we separately identified 3 major subtypes of astrocytes at the 12 h-tMCAO-system and 24 h-tMCAO-system, indicated the significant differences in the expression of genes and metabolic pathways in the astrocytes between the two time nodes after ischemic stroke, and detected the major change in the energy metabolism. These results provided a comprehensive understanding of the characteristic changes of astrocytes after ischemic stroke and explored the potential astrocytic targets for neuroprotection.
In order to study the seismic damage of reinforced concrete shear walls,based on the analysis of the current seismic damage models,a modified model with double variables is presented by using an ideal elastoplastic restoring force model of structural members.Based on the test data,deformation and cumulative hysteretic dissipation energy are analyzed for reinforced concrete shear walls under low-cyclic loading test,the parameters in the modified model are determined.The comparison between the damage value due to the maximum deformation and that due to the cumulative hysteretic dissipation energy show that the damage value due to the maximum deformation is larger than that due to dissipation energy,however,the damage caused by the cumulative hysteretic dissipation energy can not be neglected.
Objective
To evaluate the predictive values of human papilloma virus (HPV) E6/E7 mRNA test in the prognosis of patients with cervical intraepithelial neoplasia (CIN) 1.
Methods
From July 2013 to October 2014, a total of 107 cases of patients who were initially diagnosed as CIN1 by pathologic results of colposcopic cervical biopsy in Department of Gynecology, Yantaishan Hospital of Yantai were selected as research subjects. All subjects received cervical ThinPrep liquid-based cytology test (TCT), HPV DNA genotyping test and HPV E6/E7 mRNA test within one month prior to initial diagnosis of CIN1. Two-year follow-ups and once every six months were conducted on all subjects, including the re-examination of TCT, HPV DNA genotyping test and HPV E6/E7 mRNA test. And cervical biopsies were conducted on suspicious lesions. According to the results of TCT, HPV DNA genotyping test, HPV E6/E7 mRNA test and colposcopic cervical biopsy at the end of follow-up, all subjects were enrolled into negative group and continuous or progressive group, respectively. Chi-square test was used to compare the positive rates of HPV E6/E7 mRNA between two groups. Mann-Whitney U rank sum test was used to compare expression levels of HPV E6/E7 mRNA between two groups. The sensitivities and specificities of these three cervical screening methods in predicting the prognosis of CIN1 were calculated respectively. Then receiver operator characteristic (ROC) curve of HPV E6/E7 mRNA expression level in predicting the prognosis of CIN1 was drawn, and the area under ROC curve (ROC-AUC) was calculated.The optimal critical value of HPV E6/E7 mRNA expression level in predicting the prognosis of CIN1 was obtained when the Youden index reaching the maximum value.And its sensitivity and specificity were calculated. This study was approved by the Ethics Committee of Human Beings in Yantaishan Hospital of Yantai and informed consent of clinical research has been signed with every subject.
Results
①According to the results of TCT, HPV DNA genotyping test, HPV E6/E7 mRNA test and colposcopic cervical biopsy at the end of follow-up, all subjects were enrolled into negative group (n=63, the results of TCT, HPV DNA genotyping test and HPV E6/E7 mRNA test all were normal or the colposcopic cervical biopsy result was negative at the end of follow-up) and continuous or progressive group (n=44, the colposcopic cervical biopsy result was CIN1 or higher grade at the end of follow-up). There were no statistically significant differences between two groups in basic clinical data such as age and etc. (P>0.05). ②The positive rate of HPV E6/E7 mRNA and median expression level of HPV E6/E7 mRNA were 61.9% (39/63) and 3 738.4 copy/mL in continuous or progressive group, which were significantly higher than those in negative group (81.8%, 36/44) and 583.5 copy/mL, respectively), and both the differences were statistically significant (χ2=4.901, P=0.027; U=821.000, P<0.001). ③According to the results of two-year follow-up, the continuous or progressive rate of CIN in patients with HPV-16/18 positive was 50.8% (31/61), which was significantly higher than that in patients with HPV-16/18 negative (28.3%, 13/46), and the difference was statistically significant (χ2=5.512, P=0.019). The continuous or progressive rate of CIN in patients with HPV E6/E7 mRNA positive was 48.0% (36/75), which was significantly higher than that in patients with HPV E6/E7 mRNA negative (25.0%, 8/32), and the difference was statistically significant (χ2=4.901, P=0.027). The sensitivities of TCT, HPV DNA genotyping test and HPV E6/E7 mRNA qualitative test in predicting the prognosis of CIN1 were 50.0%, 70.5%, 81.8%, and the specificities were 66.7%, 52.4%, 38.1%, respectively. ④The results of ROC curve analysis of HPV E6/E7 mRNA expression level in predicting the prognosis of CIN1 showed that the ROC-AUC was 0.704 (95%CI: 0.601-0.806, P<0.001), and the optimal critical of value HPV E6/E7 mRNA expression level in predicting the prognosis of CIN1 was 2 724.0 copy/mL, and the sensitivity of HPV E6/E7 mRNA expression level in predicting continuous or progression of CIN was 54.5%, and the sensitivity was 81.0%.
Conclusions
The sensitive of HPV E6/E7 mRNA qualitative test in predicting the prognosis of CIN1 is relatively high, while the specificity of HPV E6/E7 mRNA quantitative test in predicting the prognosis of CIN1 is relatively high. HPV E6/E7 mRNA test may has clinical values in predicting the prognosis of patients with CIN1.
Key words:
Cervical intraepithelial neoplasia; Human papillomavirus; Papillomavirus E7 proteins; Genotyping; Prognosis; Female
β-Lactam/β-lactamase inhibitor is able to inactivate a wide range of β-lactamases produced by Gram-positive,Gram-negative,anaerobic and even acid-fast pathogens.Clinical experience confirms their efficacy in the empirical treatment of respiratory tract,intra-abdomina,and skin and soft tissue infections.There is evidence to suggest that they are effective in treatment of patients with neutropenic fever and nosocomial infections.β-Lactam/β-lactamase inhibitor combinations are particularly effective to treat patients with mixed infections.β-Lactamase inhibitors have gained more and more importance in treating various multi-resistant pathogens such as Acinetobacter species and Stenotrophomonas maltophilia.This review gives us a brief introduction of the research and development of β-lactamase inhibitors.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)