Background and purpose: It has been reported that activation of Notch1 could strongly inhibit proliferation of HPV (human papilloma virus)-positive HeLa cells by down-regulation of the E6 and E7 genes. The aim of this paper was to investigate the role of the Notch signaling pathway in growth arrest of EC109 cells in vitro and the molecular mechanism. Methods: EC109 cell lines, a well differentiated human ESCC (esophageal squamous cell carcinoma) cell line with HPV18-positive, was used in the study. Exogenous intracellular domain of Notch1(ICN) was transfected into cultured EC109 cells by lipofectamine transfection, the proliferation of the transfected cells was measured by an MTT assay. Cell cycle distribution was analyzed by flow cytometry. Human papilloma virus type 18 (HPV18) E6/E7 mRNA expression was detected by RT-PCR, and p53 protein expression was detected by Western blot.Results: Activation of Notchl signaling resulted in inhibition of EC109 cell proliferation with the induction of G_2/ M arrest. There was a significant difference in terms of the percentage of G_2/M phase cells among the ICN-transfected group (42.57±1.57)% and the non-transfected group (1.88±0.66)% or the empty plasmid transfected group (1.99±1.02)% (P<0.01). Down modulation of HPV18 E6/E7 gene expression and upregulation of p53 expression was (2.15±0.23) in ICN-transfected group higher than non- transfected group (0.45±0.07) and empty plasmid transfected group (0.46±0.02) (P<0.01). Conclusion: Repression of HPV18 E6/E7 expression by Notch1 signaling results in growth suppression of HPV18-positive EC109 cells with concomitant activation of p53-mediated pathways.

Objective:To explore the common risk factors of intracerebral hemorrhage(ICH) in young people and to establish a predictive model of nomogram.Methods:The relevant data of young patients with ICH (≤45 years ) hospitalized in the Department of Neurosurgery of Dezhou people's Hospital from January 2014 to August 2021 were retrospectively studied, and the young group who underwent physical examination in the Physical Examination Center of Dezhou people's Hospital at the same time were randomly selected as the control group. Analyze the risk factors that may affect cerebral hemorrhage in young people, screen the risk factors with statistical differences through single factor analysis, screen the independent risk factors according to multi factor Logistic regression analysis, construct the risk nomogram model of cerebral hemorrhage in young people, and test the efficiency, goodness of fit and benefit of the constructed model through internal validation.Results:Compared with the control group, there were statistically significant differences in family history (χ 2=115.66, P<0.001), hypertension grade( Z=17.67, P<0.001), smoking history (χ 2=33.91, P<0.001), drinking grade ( Z=4.84, P<0.001), body mass index (BMI) ( t=11.76, P<0.001), low density lipoprotein ( t=4.78, P<0.001), high density lipoprotein cholesterol ( t=5.83, P<0.001),blood glucose ( Z=5.68, P<0.001) and homocysteine ( Z=2.22, P<0.001) in the case group. Binary Logistic regression analysis showed that hypertension grade ( OR=3.457, 95%CI: 2.809-4.254, P<0.001), family history ( OR=2.871, 95%CI:1.868-4.413, P<0.001), BMI ( OR=1.093, 95%CI:1.040-1.148, P<0.001), high density lipoprotein cholesterol ( OR=0.230, 95%CI:0.111-0.480, P<0.001), blood glucose ( OR=3.457, 95%CI:2.809-4.254, P<0.001), homocysteine (O R=3.457, 95%CI:2.809-4.254, P<0.001) was an independent risk factor for intracerebral hemorrhage in young adults. The nomogram prediction model showed that BMI was 96 points, hypertension grade was 100 points, family history was 30 points, high density lipoprotein cholesterol was 76 points, homocysteine was 48 points, blood glucose was 52 points,homocysteine was 48 points and blood glucose was 52 points, respectively. The consistency coefficient of the prediction model was 0.874. The nomogram dependent ROC curve AUC was 0.891, and the corresponding sensitivity and specificity were 74.5% (263/353) and 89.7% (437/487), respectively, a nomogram model was established with good diagnostic efficiency. Conclusion:The nomogram model established in this study can predict the probability of intracerebral hemorrhage in high-risk population, and take intervention measures as early as possible to prevent the occurrence of intracerebral hemorrhage in young people.

The rapid progress on immunotherapy and targeted therapy has brought long-term survival benefits for locally advanced non-small cell lung cancer (NSCLC). The oncology community has also paid more attention to the local treatment for advanced NSCLC, especially for patients with limited metastatic lesions, also known as oligo-metastasis. Many studies have reported that oligo-metastatic NSCLC patients could benefit from the combination of local and systematic treatment, and even to be cured. In recent years, with the advances in radiation technology, stereotactic body radiation therapy (SBRT) has achieved precise high-dose radiotherapy for small target tumors. Currently, SBRT has been widely applied in the treatment of inoperable early lung cancer, and its application value and safety in patients with advanced lung cancer are also being actively explored. In this article, the research status, progress and future development direction of SBRT in the treatment of oligo-metastatic NSCLC were discussed.

Objective To analyze the main active components and potential molecular mechanism of Sophora flavescens against breast cancer based on network pharmacology and molecular docking. Methods The chemical constituents were collected and screened by TCMSP, ETCM database and literature review. The targets of active ingredients were predicted by Swiss Target Prediction database. Breast cancer-related targets were collected by GeneCards, TTD, Drugbank and OMIM. The anti-breast cancer targets of Sophora flavescens were screened by Venny 2.1.0 software. Cytoscape software was used to construct the network diagram of Sophora flavescens-key active ingredients-targets. STRING database was used to analyze the common targets, and PPI network diagram was constructed. GO function enrichment analysis and KEGG pathway enrichment analysis of key target proteins were performed by DAVID database and Hiplot online platform. Schrodinger software was used to calculate the molecular docking between the active ingredients and targets. Molecular biological methods were used to verify the key targets. Results A total of 36 active components with clear structures were screened from Sophora flavescens. 70 anti-breast cancer targets of Sophora flavescens were screened out. 12 core targets including EGFR, AKT1, ESR1, SRC, CYP19A1, AR and ABCB1 participate in endocrine resistance, EGFR tyrosine kinase inhibitors and estrogen signaling pathways in breast cancer. Moreover, the docking score between the core component and the key target AR is the highest. In vitro experiments showed that the extract of Sophora flavescens can inhibit the proliferation of breast cancer cells, induce cell apoptosis and up-regulate AR protein expression. Conclusion It was revealed that Sophora flavescens plays an anti-breast cancer role by regulating complex biological processes through multiple components acting on multiple targets and signaling pathways. The upregulation of AR protein by Sophora flavescens may become a new therapeutic strategy for the treatment of breast cancer.

Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.
Humans ; 3' Untranslated Regions ; Arthritis, Gouty/genetics* ; Interleukin-1beta/genetics* ; Interleukin-8 ; Luciferases ; MicroRNAs/genetics* ; Tumor Necrosis Factor-alpha