Objective To investigate the effect of hnRNPAB overexpression on epithelial-mesenchymal transformation(EMT) and its molecular mechanism using human colorectal cancer line SW480 and HT29. Methods SW480 and HT29 cells were infected with lentivirus overexpressing hnRNPAB and negative control virus to generate the corresponding cell lines in experimental group (SW480-hnRNPAB, HT29-hnRNPAB) and control group (SW480-NC, HT29-NC). To quantify the levels of hnRNPAB and EMT-related indicators (E-cadherin, N-cadherin and vimentin), RT-qPCR and Western blotting were used. Cell migration was measured using the scratch assay. Cell invasion was evaluated using the Transwell assay. Western blotting was used to detect the expression levels of Wnt/β-catenin signaling key indicators WNT3A, WNT5A and β-catenin. Results Compared with control group, the expression levels of hnRNPAB mRNA and protein in experimental group significantly increased, and the differences were statistically significant (P<0.01). The scratch healing rates in experimental group were significantly higher than that in control group (SW480: 19.6%±0.90% vs. 2.23%±0.80%, P<0.01; HT29: 40.30%±0.70% vs. 6.40%±0.06%, P<0.01). The number of Transwell cells was significantly higher than that in control group [SW480: (315.0±6.7) cells vs. (62.0±4.3) cells, P<0.01; HT29:(289.0±7.2) cells vs. (54.0±5.2) cells, P<0.01]. Compared with control group, the epithelial cell marker E-cadherin mRNA and protein expression levels in experimental group significantly decreased. As expected, the mesenchymal cell markers N-cadherin and vimentin mRNA and protein levels significantly increased, and the differences were statistically significant (P<0.01). Compared with control group, the expressions of WNT3A, WNT5A and β-catenin protein in experimental group significantly increased (P<0.01). Conclusions The overexpression of hnRNPAB could induce EMT of human colorectal cancer SW480 and HT29, demonstrated by enhanced cell migration and invasion ability. The mechanism may be related to the activation of the Wnt/β-catenin signaling pathway.

Intervertebral disc degeneration (IDD) is a common orthopedic disease characterized by reduction of nucleus pulposus cells and degradation of extracellular matrix. Its specific pathogenesis is not clear. The current treatment can only improve the clinical symptoms of patients, but can not delay or reverse the process of degeneration. Therefore, to find an effective method to repair IDD has become the main goal of current research. In recent years, exosomes have gradually become a research hotspot in the field of regenerative medicine. Exosomes carrying a large number of nucleic acids, proteins, lipids, cytokines and other bioactive molecules participate in the information transmission between different cells and play an important role in regulating the biological functions of receptor cells. Studies have confirmed that exosomes can inhibit the apoptosis and inflammatory reaction of nucleus pulposus cells, promote the proliferation and regeneration of nucleus pulposus cells, and have the potential to cure IDD. In this paper, the characteristics and functions of exosomes from different cell sources and its effect and mechanism in IDD repair were summarized, in order to provide reference for the subsequent studies.

Objective To explore the impact of severe calcification on the abnormal hemodynamics based on CT-fractional flow reserve (CT-FFR) diagnosis, and evaluate the diagnostic significance of pericoronary fat attenuation index (FAI) on the abnormal hemodynamics of severely calcified coronary artery. Methods The clinical data of patients were retrospectively analyzed who underwent a coronary computed tomography angiography (CCTA) examination within one month before an invasive FFR examination from January 2017 to December 2019 in the First Medical Center of Chinese PLA General Hospital. Regarding invasive FFR≤0.8 as the gold standard of hemodynamically abnormal coronary artery disease (CAD), patients were assigned to FFR≤0.8 group and FFR>0.8 group. The coronary artery calcium score (CACS), degree of major coronary branch stenosis, pericoronary FAI and CT-FFR were measured and compared. Invasive FFR≤0.8 represents the presence of lesion-specific hemodynamic significant CAD. According to the quartiles of CACS, patients were further divided into mildly-moderately calcified (1st-3rd quartiles) and severely calcified (4th quartile) stratification. The diagnostic efficacy for abnormal coronary hemodynamics was analyzed only with CT-FFR and combined with pericoronary FAI detection between the two groups. Results A total of 99 patients with 124 main coronary arteries were included (37 in FFR≤0.8 group, and 87 in FFR>0.8 group). In terms of vascular characteristics, statistically significant differences existed between FFR≤0.8 group and FFR>0.8 group in CACS (85.80, 95%CI 6.750~0.977 vs. 42.50, 95%CI 0.600~110.200, P<0.05), degree of major coronary branch stenosis (63.8%±9.9% vs. 57.6%±9.5%, P<0.01), pericoronary FAI(–73.3±9.5 vs. –80.6±7.5, P<0.01) and CT-FFR (0.77±0.04 vs. 0.86±0.04, P<0.01). The diagnostic efficacy of CT-FFR was lower for severe calcified vessels than for the vessels with mild to moderate calcification (AUC=0.767, 95%CI 0.581~0.899 vs.AUC=0.936, 95%CI 0.865~0.976, P<0.05), while the pericoronary FAI showed good diagnostic efficacy for the severe calcified vessels (AUC=0.850, 95%CI 0.676~0.952). CT-FFR combined with pericoronary FAI improved the diagnostic efficacy than using CT-FFR alone (AUC=0.917, 95%CI 0.760~0.985 vs. AUC=0.767, 95%CI 0.581~0.899, P=0.046). Conclusion For severe calcified vessels, the effectiveness declined of CT-FFR in the diagnosis of significant coronary ischemia, while combined implementation of FAI may improve the diagnosis of CAD with abnormal hemodynamics.

Breast cancer is the most common malignant tumor in the world. Endocrine therapy is an important treatment for HR positive breast cancer, and its drugs are mainly divided into premenopausal estrogen receptor antagonists and postmenopausal aromatase inhibitors, but drug resistance has become a major challenge in endocrine therapy for breast cancer. This article reviews the drug resistance mechanism and the latest research results of endocrine therapy in premenopausal and postmenopausal breast cancer from the aspects of gene regulation, estrogen and coregulatory cofactor, growth factor signal pathway, cell cycle regulation,autophagy and apoptosis, non-coding RNA regulation, immune surveillance, etc., in order to provide a new basis for clinical solution of endocrine therapy resistance in breast cancer.

Objective To investigate the effect of psoralen on the degeneration of human nucleus pulposus cells (HNPCs)induced by interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) and its mechanism. Methods HNPCs were cultured in vitro, and HNPCs were stimulated by 10 ng/ml IL-1β and 50 ng/ml TNF-α for 24 hours to induce degeneration. Cells were divided into control group, IL-1β+TNF-α group, psoralen (10 μmol/L, 25 μmol/L and 50 μmol/L) group, psoralen (25 μmol/L) + S-phase kinase-associated protein 2 (SKP2) interference or over-expression group, psoralen + parathyroid hormone-related protein (PTHrP)recombinant protein (100 nmol/L) group, psoralen + PTHrP recombinant protein (100 nmol/L) + silent information regulator 1 (SIRT1) activator SRT1720 (1 μmol/L) group. The apoptosis of nucleus pulposus cells was detected by flow cytometry; the levels of IL-6, MMP-3 and MMP-13 in nucleus pulposus cells were detected by ELISA; the level of reactive oxygen species (ROS)in nucleus pulposus cells was detected by the DCFDA probe method. Western blotting was used to detect the expression levels of SKP2, PTHrP, SIRT1 and extracellular matrix (ECM) related protein [type II collagen (COL II) and proteoglycan protein]. Co-immunoprecipitation (Co-IP) experiment was used to verify the binding of SKP2 and PTHrP, ubiquitination experiment was used to analyze the effect of psoralen on SKP2-mediated PTHrP ubiquitination. Results Psoralen significantly inhibited cell apoptosis,the production of IL-6, MMP-3, MMP-13 and ROS (P<0.05 or P<0.01), and promoted the expression of SKP2 and ECM-related proteins of HNPCs after IL-1β and TNF-α induction in a dose-dependent manner (P<0.05). Compared with psoralen + scramble group, the expression levels of SKP2 and ECM-related proteins were significantly reduced (P<0.05), and the apoptosis rate, the levels of IL-6, MMP-3, MMP-13 and ROS were significantly increased in psoralen + SKP2 interference group (P<0.05 or P<0.01).The results of the Co-IP experiment showed that SKP2 is directly bound to PTHrP. The results of the ubiquitination experiment showed that, compared with psoralen + empty vector group, the expression level of PTHrP protein was significantly decreased, and the expression level of SKP2 protein was significantly increased in psoralen + SKP2 over-expression group (P<0.05). Compared with psoralen group, the expression levels of SIRT1 and ECM-related proteins were significantly reduced (P<0.05), and the apoptosis rate,the levels of IL-6, MMP-3, MMP-13 and ROS were significantly increased in psoralen + PTHrP recombinant protein group (P<0.05).Compared with psoralen + PTHrP recombinant protein group, the expression level of PTHrP protein did not change significantly(P>0.05), and the expression levels of SIRT1 and ECM-related proteins were significantly increased (P<0.05), the apoptosis rate,the levels of IL-6, MMP-3, MMP-13 and ROS were significantly decreased in psoralen + PTHrP recombinant protein + SRT1720 group (P<0.05). Conclusion Psoralen can promote SKP2-mediated PTHrP ubiquitination, activate SIRT1, and alleviate NP cell apoptosis in an inflammatory environment.

Objective To explore the relationship between platelet function and disease progression and prognosis in patients with cerebral hemorrhage without antiplatelet agents. Methods A retrospective analysis was performed on the clinical data of 129 patients with intracerebral hemorrhage who were admitted to the Neurosurgical Department, the First Affiliated Hospital of Chongqing Medical University from January 2015 to December 2019. These patients were divided into two groups: rebleeding group after intracerebral hemorrhage (n=53) and non-rebleeding group (n=76). The relation of thrombelastograph parameters including R value, K value, Angle of view, and the inhibition rates of arachidonic acid (AA) and adenosine diphosphate (ADP) under the condition without use of antiplatelet drugs at admission and their correlation with Glasgow Coma Scale score were compared between the two groups. Results The AA inhibition rate (P=0.015) and ADP inhibition rate (P=0.025) in rebleeding group were statistically higher than those in non-rebleeding group. AA inhibition rate of platelet function (P=0.022) and ADP inhibition rate (P=0.030) in rebleeding death group were statistically higher than those in survival group. AA inhibition rate (r=–0.183,P=0.038) and ADP inhibition rate (r=–0.175, P=0.047) were negatively correlated with Glasgow Coma Scale score. Conclusions Thrombelastographic detection of platelet function can be used as an early warning indicator to assist the assessment of the risk of rebleeding and prognosis in patients with intracerebral hemorrhage.

Objective To explore the short-term efficacy and safety of golimumab (GLM) for treatment of refractory non-infectious uveitis. Methods Nonrandomized retrospective case series. Forty-six patients in Department of Ophthalmology Beijing Chaoyang Hospital from October 2018 to December 2019 with different types of uveitis that were resistant to treatment with previous immunosuppressors were included in this study. All the patients were treated with GLM (50 mg every four weeks) during at least 3 months. Clinical evaluation and treatment-related side effects were assessed in all included patients. Results At the end of follow up, ocular inflammation was controlled or relieved in 34 patients, the response rate was 73.91%.There was a statistically significant improvement in mean best corrected visual acuity (0.22 vs. 0.26, P=0.002). GLM therapy achieved complete control of inflammation in 9 patients (19.57%). GLM was continuously used in 17 patients (36.96%) without inflammation recurrence, including single GLM treatment in 14 patients, and combination with conventional immunosuppressors in 3 patients. The types of conventional immunosuppressors [M(Q₁, Q₃)] decreased from 2(2, 3) to 1(1, 2) (P<0.001) after GLM treatment. The dosage of prednisone decreased from 38 mg/d [(30, 45) mg/d] at baseline to 8 mg/d [(5, 15) mg/d](P<0.001). The systemic adverse effects associated with GLM therapy were observed in 4 patients, including bacterial pneumonia in 1 patient, anaphylactic reaction in 2 patients, and transaminase elevation in 1 patient. Conclusion GLM can effectively reduce the recurrence of non-infectious refractory uveitis, improve patients' vision, and reduce the combined use of glucocorticoid and immunosuppressors.

Ferroptosis suppressor protein 1 (FSP1), confirmed as a ferroptosis-resistant factor recently, plays a key role in the oncogenesis and progress of human diseases, such as breast cancer, ovarian cancer, lung cancer, hepatocellular carcinoma,melanoma, lymphoma, leukemia, copper resistance, severe acute pancreatitis, and diabetes. FSP1 is regarded as a double-edged sword according to previous studies. Mechanically, FSP1 triggers caspase-independent apoptosis via its C-terminal fragments,nuclear translocation, or over-expression, and inhibits ferroptosis through FSP1-CoQ₁₀-NAD(P)H axis, being independent of the glutathione (GSH)-GPX4 axis. The research progress in action mechanism of FSP1 in human diseases is briefly described in this review for providing novel preventative and therapeutic target molecules for human diseases.

Objective To investigate the effect of HOX transcriptional antisense RNA (HOTAIR) targeted regulating miR-424 expression on the biological behavior of ovarian cancer cells. Methods Sixty ovarian cancer samples from patients with ovarian cancer and randomly matched 60 benign ovarian tumor tissues were collected during January to June 2018 in the Third Affiliated Hospital of Zunyi Medical University. q-PCR was used to detect the expression of HOX transcript antisense RNA (HOTAIR) in ovarian cancer and adjacent tissues, and analyze the survival rate of ovarian cancer patients with different HOTAIR expression levels, analyze the relationship between the expression level of HOTAIR and the clinicopathological parameters of ovarian cancer patients. A2780 ovarian cancer cells were transfected with small interfering RNA (siRNA) to construct siRNA-HOTAIR (si-HOTAIR) cells as the experimental group, and A2780 ovarian cancer cells transfected with siRNA-NC (si-NC) cells were used as the control group. Dual fluorescence was used to detect the interaction between HOTAIR and miR-424 by the enzyme reporter gene,A2780 cells were used in scratch test to detect the change in the migration ability of ovarian cancer cells after inhibiting HOTAIR,Transwell invasion test was used to detect the change in the invasive ability of ovarian cancer cells after inhibiting HOTAIR, and Flow cytometry was performed to analyze the changes of ovarian cancer cell apoptosis after inhibiting HOTAIR. The nude mouse subcutaneous tumor formation experiment was used to detect the effect of inhibiting HOTAIR on the tumor size and volume of ovarian cancer cells. Results qPCR results showed that the expression of HOTAIR increased significantly in ovarian cancer tissues than in benign ovarian tumor tissues [(58.64±6.32) vs. (6.35±0.02), P<0.05]. The long term survival rate was lower in patients with high expression level of HOTAIR than in patients with low expression level of HOTAIR. Dual-Luciferase reporter gene system showed that HOTAIR can specifically bind to the 3'-UTR of miR-424 [(0.42±0.08) vs. (1.06±0.11), P<0.05]. Scratch test and Transwell invasion test showed that, compared with control group, inhibiting the expression of HOTAIR can inhibit the migration behavior [(21.21±3.08) μm vs. (92.34±8.65) μm, P<0.05] and invasion behavior of ovarian cancer cells in experimental group(28.63%±5.59% vs. 275.36%±21.62%, P<0.05). The results of flow cytometry showed that inhibiting the expression of HOTAIR can enhance the apoptosis of ovarian cancer cells in experimental group (30.2%±2.12% vs. 7.31%±2.01%, t=10.64, P<0.05). In vivo tumor formation experiments in nude mice showed that, compared with control group, the tumor volume and weight of tumor-bearing mice correspondingly decreased [(0.85±0.06) cm³ vs. (3.05±0.28) cm³, t=13.41, P<0.05; (1.12±0.08) g vs. (2.91±0.19) g,t=11.64, P<0.05] after inhibiting HOTAIR expression. Conclusion lncRNA HOTAIR can target miR-424 to regulate the apoptosis, migration and invasion of ovarian cancer cells.

Objective To explore the correlation of the serum C-reactive protein/albumin ratio (CRP/ALB, CAR) and homocysteine/high-density lipoprotein cholesterol (HCY/HDL-C) to the morbid change of coronary artery disease. Methods A total of 577 patients who underwent coronary angiography in the Department of Cardiology of the 904th Hospital of PLA Joint Logistics Support Force from January 2018 to December 2019 were divided into two groups according to the results of coronary angiography: non-coronary heart group (n=245) and coronary atherosclerotic heart disease group (coronary heart disease group,n=332). The coronary heart disease group was further divided into two subgroups: mild coronary artery disease subgroup (Gensini score <30, n=183) and severe coronary artery disease subgroup (Gensini score ≥30, n=149). The serum levels of CRP, ALB, HCY,HDL-C and other indicators of patients in each group were detected, and CAR and HCY/HDL-C were calculated, and then the logistic regression analysis, Pearson correlation analysis and receiver operating characteristic (ROC) curve analysis were carried out to analyze the independent risk factors for coronary heart disease and severe coronary artery lesion. Results The levels of CAR and HCY/HDL-C were significantly higher in coronary heart disease group than those in non-coronary heart disease group with statistically significant difference (P<0.05). Multivariate logistic regression analysis showed that CAR, HCY/HDL-C, age, hypertension, and gender were the independent risk factors for coronary heart disease and severe coronary artery disease. Pearson correlation analysis showed that CAR and HCY/HDL-C were positively correlated with Gensini score (r=0.427, P<0.01; r=0.247,P<0.01). The results of ROC curve analysis showed that CAR, HCY/HDL-C and both their combination had predictive values for severe coronary heart disease, and the AUC of combined the both factors was statistically higher than that of any single factor alone(P<0.05). Conclusions Elevated levels of CAR and HCY/HDL-C may predict the severe coronary artery disease. The diagnostic value of combined the two factors is better than a single factor alone, so can be used for the diagnosis and condition evaluation of coronary artery disease.