Background and purpose:Because of the heterogeneity of cancers,different patients with the same kind of cancer have different sensitivity for cytotoxic drugs.Newly developed ATP chemosensitivity assays(ATPTCA) offer the opportunity for individualized therapy and have shown promising results compared to standard regimens.We explored the feasibility of the ATP-Tumor Chemosensitivity Assay(ATP-TCA) applied in the treatment of ovarian cancer with chemotherapy,and evaluate the in vitro sensitivity of fresh specimens of ovarian cancer to five cytotoxic drugs.Methods:ATP-TCA was used to detect the sensitivity rate of 24 fresh specimens of ovarian cancer to five cytotoxic drugs as follows: paclitaxel(TAX),gemcitabine(GEM),doxorubicin(ADM),topotecan(TPT),cisplatin(DDP).Results:23 of 24 specimens((95.83%)) can be evaluated by ATP-TCA,the sensitive rates of ATP-TCA was 91.30% for TAX,86.96% for GEM,65.22% for ADM,47.83% for TPT and 21.74% for DDP,respectively.Conclusions:ATP-TCA was a sensitive、reliable and standardized method for the evaluation of tumor chemosensitivity,it ts worthwhile to investigate further for the application screening anticancer agents in chemotherapy of ovarian cancer.

MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs with regulatory functions. Traditionally, miRNAs are thought to play a negative regulatory role in the cytoplasm by binding to the 30UTR of target genes to degrade mRNA or inhibit translation. However, it remains a challenge to interpret the potential function of many miRNAs located in the nucleus. Recently, we reported a new type of miRNAs present in the nucleus, which can activate gene expres-sion by binding to the enhancer, and named them nuclear activating miRNAs (NamiRNAs). The discovery of NamiRNAs showcases a complementary regulatory mechanism of miRNA, demon-strating their differential roles in the nucleus and cytoplasm. Here, we reviewed miRNAs in nucleus to better understand the function of NamiRNAs in their interactions with the enhancers. Accord-ingly, we propose a NamiRNA–enhancer–target gene activation network model to better under-stand the crosstalk between NamiRNAs and enhancers in regulating gene transcription. Moreover, we hypothesize that NamiRNAs may be involved in cell identity or cell fate determina-tion during development, although further study is needed to elucidate the underlying mechanisms in detail.

Objective To construct a traditional Chinese medicine(TCM)knowledge base using knowl-edge graph based on deep learning methods,and to explore the application of joint models in intelligent question answering systems for TCM. Methods Textbooks Prescriptions of Chinese Materia Medica and Chinese Materia Medicawere applied to construct a comprehensive knowledge graph serving as the founda-tion for the intelligent question answering system.In the study,a BERT+Slot-Gated(BSG)deep learning model was applied for the identification of TCM entities and question inten-tions presented by users in their questions.Answers retrieved from the knowledge graph based on the identified entities and intentions were then returned to the user.The Flask framework and BSG model were utilized to develop the intelligent question answering sys-tem of TCM. Results A TCM knowledge map encompassing 3 149 entities and 6 891 relational triples based on the prescriptions and Chinese materia medica was drawn.In the question answer-ing test assisted by a question corpus,the F1 value for recognizing entities when answering 20 types of TCM questions was 0.996 9,and the accuracy rate for identifying intentions was 99.75%.This indicates that the system is both feasible and practical.Users can interact with the system through the WeChat Official Account platform. Conclusion The BSG model proposed in this paper achieved good results in experiments by increasing the vector dimension,indicating the effectiveness of the joint model method and providing new research ideas for the implementation of intelligent question answering sys-tems in TCM.

With the widespread use of Internet, the amount of data in the field of traditional Chinese medicine (TCM) is growing exponentially. Consequently, there is much attention on the collection of useful knowledge as well as its effective organization and expression. Knowledge graphs have thus emerged, and knowledge reasoning based on this tool has become one of the hot spots of research. This paper first presents a brief introduction to the development of knowledge graphs and knowledge reasoning, and explores the significance of knowledge reasoning. Secondly, the mainstream knowledge reasoning methods, including knowledge reasoning based on traditional rules, knowledge reasoning based on distributed feature representation, and knowledge reasoning based on neural networks are introduced. Then, using stroke as an example, the knowledge reasoning methods are expounded, the principles and characteristics of commonly used knowledge reasoning methods are summarized, and the research and applications of knowledge reasoning techniques in TCM in recent years are sorted out. Finally, we summarize the problems faced in the development of knowledge reasoning in TCM, and put forward the importance of constructing a knowledge reasoning model suitable for the field of TCM.

OBJECTIVETo investigate the mechanisms by which retinoic acid-induced gene G (RIG-G) protein regulates p21 gene expression.

METHODSWestern blot was used to detect the effects of RIG-G protein overexpression on p21 protein expression level in leukemia cell line NB4 cells and the phosphorylation of both c-Jun and JNK in U937 cells. The c-Jun expression plasmid and p21 gene promoter-containing reporter plasmid were co-transfected into 293T cells, to explore the regulatory effect of c-Jun protein on p21 gene expression by luciferase reporter assay.

RESULTSWestern blot showed that the overexpression of RIG-G protein significantly upregulated p21 protein level in the NB4 cells, and the level of p21 protein largely increased along with the induction of endogenous RIG-G protein during the differentiation of NB4 cells treated by all-trans retinoic acid (ATRA). Moreover, the phosphorylation of both c-Jun and JNK decreased in RIG-G-overexpressing U937 cells while total c-Jun and JNK proteins remained unchanged. After using the JNK inhibitor SP600125 to block JNK phosphorylation, the level of c-Jun phosphorylation was still dramatically reduced in the RIG-G-overexpressing U937T-RIG-G cells, compared with the control U937T-pTRE cells. These results indicated that the inhibitory effect of Rig-G protein on c-Jun phosphorylation could not only be through the JNK pathway, but also via some JNK-independent pathways. Luciferase reporter assay showed that when 0.1, 0.5, 1.0 and 2.0 µg c-Jun-expressing plasmids were respectively transfected into 293T cells, compared with the empty vector-transfected group, the relative luciferase activities were (83.0 ± 1.7)%, (73.7 ± 0.7)%, (68.9 ± 0.9)% and (64.1 ± 0.9)%, indicating that the transcriptional activity of p21 gene could be inhibited by c-Jun protein.

CONCLUSIONSRIG-G protein may suppress the phosphorylation of c-Jun protein through different signal pathways, thereby increasing the expression of p21 gene, arresting the cell cycle and inhibiting the cell growth in U937 cells.

Cell Cycle ; Cell Differentiation ; Cell Line ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; metabolism ; GTP-Binding Proteins ; genetics ; metabolism ; Genes, Reporter ; Phosphorylation ; Signal Transduction ; Transfection ; Tretinoin ; metabolism ; Up-Regulation