Objective To investigate the diagnostic value of low field MRI for adenomyosis. Methods MRI features of adenomyosis pathologically proved in 18 cases were retrospectively analysed.Results 15 cases were diffusive adenomyosis,the junctional zones of uterus were exteusive thickened to 12.0～32.6 mm,mean 16.2 mm,diffusive high signal intensity distributed over in myometrium which was low signal intensity in 11 cases,it was typical “snowing sign”,lower signal intensity in the myometrium in another 4 cases on T 2WI and fat-suppression imaging. A little high signal intensity was found in 6 cases on T 1WI. 3 cases were focal adenomyosis(adenomyoma), 4 lesions totally. The adenomyoma’s boundaries were not distinct and their shapes were roundish or irregular. The lesions were low signal intensity or diffusive high signal intensity distributed in the low signal intensity fields on T 2WI and fat-suppression imaging. A little high signal intensity was found in 2 lesions on T 1WI. Conclusion T 2WI and fat-suppression imaging of low field MRI are very useful techniques of the diagnosis of adenomyosis.

Objective To explore the protein expression of p53 and PTEN in osteosarcoma and the relationship between them and the three-year survival ratios of osteosarcoma patients.Methods The protein expression of p53 and PTEN was detected using immunohistochemical methods in 53 cases of osteosarcoma proved by surgery and pathology. Results There was significant difference between the both kind of relationship with the protein expression of PTEN and the three-year survival ratios of osteosarcoma patients who had negative expression of p53. There was no significant difference between the both kind of relationship with the protein expression of PTEN and the three-year survival ratios of osteosarcoma patients who had positive expression of p53. PTEN expression,which was analysed by logistic regression, was entered the regression model ,but p53 expression was not. Conclusion PTEN expression is more important than p53 expression in predicting the prognosis of the patient with osteosarcoma.

Objective:To investigate the effects of different lipid-lowering regimens on blood lipids, endothelial function and safety in patients with unstable angina.Methods:Patients who admitted to Henan Provincial People's Hospital for unstable angina from September 2018 to May 2019 were randomly (random number) divided into the conventional treatment group, intensive statin group and intensive lipid-lowering group. Follow-up was performed at 1, 3, and 6 months after treatment according to the predetermined lipid-lowering regimen. Assessments included lipid profile, liver function, muscle enzymes, hypersensitive C-reactive protein (hs-CRP), endothelial function (reactive hyperemia index, RHI), ischemic events, myalgia, and discontinuation. The differences of the follow-up indicators among the three groups were analyzed.Results:A total of 375 patients were enrolled and randomly divided into three groups, 125 patients in each group. There were no significant differences in demographic data and medication among the three groups. At the 1st month, the low density lipoprotein cholesterin (LDL-C) compliance rate of the intensive statin group was significantly higher than those in the conventional treatment group ( χ2=3.939, P=0.047) and the intensive lipid-lowering group ( χ2=4.63, P=0.031). At the 3rd month, the reductions of LDL-C in the intensive statin group and the intensive lipid-lowering group were significantly better than that in the conventional treatment group( P<0.01). At the 6th month, the reduction rate of LDL-C in the intensive lipid-lowering group was higher than that in the intensive statin group ( q=4.332, P<0.01). At the 1st month, the improvement of hs-CRP and RHI in the intensive statin group was significantly better than that in the conventional treatment group( q=4.133, P<0.05). From the 3rd month of treatment, the incidence of cardiovascular events in the intensive statin group and the intensive lipid-lowering group showed a tendency to decrease compared with the conventional treatment group, but no statistically significant difference was found. At the 6th months of treatment, the withdrawal rates were significantly higher in the intensive statin group and the intensive lipid-lowering group than that in the conventional treatment group (χ 2=4.488, P=0.03 and χ2=5.039, P=0.02). There were no significant differences in the ratio of liver enzyme and muscle enzyme elevation and the incidence of myalgia among the three groups (all P>0.05). Conclusions:Intensive statin therapy can make LDL-C reach the standard in patients with unstable angina pectoris as soon as possible, significantly improve inflammation indicators and endothelial function, and has good safety.

Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.

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A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest.
Drug Delivery Systems ; Proteins ; Transcriptome

Metastasis is crucial for the mortality of non-small cell lung carcinoma (NSCLC) patients. The epithelial-mesenchymal transition (EMT) plays a critical role in regulating tumor metastasis. Glioma-associated oncogene 1 (Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein, we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.

Digital guided therapy (DGT) has been advocated as a contemporary computer-aided technique for treating endodontic diseases in recent decades. The concept of DGT for endodontic diseases is categorized into static guided endodontics (SGE), necessitating a meticulously designed template, and dynamic guided endodontics (DGE), which utilizes an optical triangulation tracking system. Based on cone-beam computed tomography (CBCT) images superimposed with or without oral scan (OS) data, a virtual template is crafted through software and subsequently translated into a 3-dimensional (3D) printing for SGE, while the system guides the drilling path with a real-time navigation in DGE. DGT was reported to resolve a series of challenging endodontic cases, including teeth with pulp obliteration, teeth with anatomical abnormalities, teeth requiring retreatment, posterior teeth needing endodontic microsurgery, and tooth autotransplantation. Case reports and basic researches all demonstrate that DGT stand as a precise, time-saving, and minimally invasive approach in contrast to conventional freehand method. This expert consensus mainly introduces the case selection, general workflow, evaluation, and impact factor of DGT, which could provide an alternative working strategy in endodontic treatment.
Humans ; Consensus ; Endodontics/methods* ; Tooth ; Printing, Three-Dimensional ; Dental Care ; Cone-Beam Computed Tomography ; Root Canal Therapy