OBJECTIVE: To investigate the effect of miR-4443 expression on migration and invasion of breast cancer. METHODS: We examined the expression of miR-4443 in breast carcinoma in situ and paired adjacent tissues from 3 breast cancer patients with high-throughput sequencing and verified the results using TCGA database. We also detected miR-4443 expressions using real-time quantitative PCR (RT-qPCR) in low invasive and highly invasive breast cancer cells (MCF-7 and MDA-MB-231 cells, respectively). The changes in apoptosis, migration and invasion of MCF-7 and MDA-MB-231 cells after transfection with miR-4443 mimics, mimics-NC, miR-4443 inhibitor or inhibitor-NC were analyzed using flow cytometry, wound healing assay and Transwell invasion assay. The target gene of miR-4443 was predicted by bioinformatics software and validated by a dual luciferase reporter gene system. RT-qPCR and Western blotting were performed to detect the expression of recombinant human phosphatidyl ethanolamine binding protein 1 (PEBP1) in the transfected cells. RESULTS: The expression of miR-4443 was significantly higher in the breast cancer tissues than in the adjacent tissues ( CONCLUSIONS MiR-4443 promotes the migration and invasion of breast cancer cells by inhibiting the expression of PEBP1, suggesting the possibility of suppressing miR-4443 expression as a potential therapeutic strategy for breast cancer.
Breast Neoplasms/genetics* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; MicroRNAs/genetics* ; Neoplasm Invasiveness/genetics* ; Phosphatidylethanolamine Binding Protein

OBJECTIVETo investigate the neuroprotective effects of glycyrrhizin (Gly) as well as its effect on expression of high-mobility group box 1 (HMGB1) in rats after traumatic brain injury (TBI).

METHODSMale Sprague-Dawley rats were randomly divided into three groups: sham group, TBI group, and TBI+Gly group (n=36 per group). Rat TBI model was made by using the modified Feeney's method. In TBI+Gly group, Gly was administered intravenously at a dosage of 10 mg/kg 30 min after TBI. At 24 h after TBI, motor function and brain water content were evaluated. Meanwhile, HMGB1/HMGB1 receptors including toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nuclear factor-κB(NF-κB) signaling pathway and inflammatory cytokines in the injured brain tissues were detected using quantitative real-time polymerase chain reaction, western blot, electrophoretic mobility shift assay and enzyme-linked immunosorbent assay. Furthermore, HMGB1, RAGE and TLR4 immunohistochemistry and apoptosis were analyzed.

RESULTSBeam walking performance impairment and brain edema were significantly reduced in TBI+Gly group compared with TBI group; meanwhile, the over-expressions of HMGB1/HMGB1 receptors (TLR4 and RAGE)/NF-κB DNA-binding activity and inflammatory cytokines were inhibited. The percentages of HMGB1, RAGE and TLR4-positive cells and apoptotic cells were respectively 58.37% ± 5.06%, 54.15% ± 4.65%, 65.50% ± 4.83%, 52.02% ± 4.63% in TBI group and 39.99% ± 4.99%, 34.87% ± 5.02%, 43.33% ± 4.54%, 37.84% ± 5.16% in TBI+Gly group (all P<0.01 compared with TBI group).

CONCLUSIONGly can reduce secondary brain injury and improve outcomes in rat following TBI by down-regulation of HMGB1/HMGB1 receptors (TLR4 and RAGE)/NF-κB-mediated inflammatory responses in the injured rat brain.

Animals ; Brain Injuries ; drug therapy ; Glycyrrhizic Acid ; pharmacology ; therapeutic use ; HMGB1 Protein ; metabolism ; Male ; Neuroprotective Agents ; therapeutic use ; Rats ; Rats, Sprague-Dawley

Objective:To construct a prognosis associated micro RNA(miRNA) prediction model based on bioinformatics analysis and evaluate its application value in pancreatic cancer patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 171 pancreatic cancer patients from the Cancer Genome Atlas (TCGA) (https: //cancergenome.nih.gov/) between establishment of database and September 2017 were collected. There were 93 males and 78 females, aged from 35 to 88 years, with a median age of 65 years. Of the 171 patients, 64 had complete clinicopathological data. Patients were allocated into training dataset consisting of 123 patients and validation dataset consisting of 48 patients using the random sampling method, with a ratio of 7∶3. The training dataset was used to construct a prediction model, and the validation dataset was used to evaluate performance of the prediction model. Nine pairs of miRNA sequencing data (GSE41372) of pancreatic cancer and adjacent tissues were downloaded from Gene Expression Omnibus database. The candidate miRNAs were selected from differentially expressed miRNAs in pancreatic cancer and adjacent tissues for LASSO-COX regression analysis based on the patients of training dataset. A prognosis associated miRNA prediction model was constructed upon survival associated miRNAs which were selected from candidate differentially expressed miRNAs. The performance of prognosis associated miRNA prediction model was validated in training dataset and validation dataset, the accuracy of model was evaluated using the area under curve (AUC) of the receiver operating characteristic curves and the efficiency was evaluated using the consistency index (C-index). Observation indicarors: (1) survival of patients; (2) screening results of differentially expressed miRNAs; (3) construction of prognosis associated miRNA model; (4) validation of prognosis associated miRNA model; (5) comparison of clinicopathological factors in pancreatic cancer patients; (6) analysis of factors for prognosis of pancreatic cancer patients; (7) comparison of prediction performance between prognosis associated miRNA model and the eighth edition TNM staging. Measurement data with normal distribution were represented as Mean± SD, comparison between groups was analyzed by the student- t test, and comparison between multiple groups was analyzed by the AVONA. Measurement data with skewed data were represented as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Ordinal data were analyzed using the rank sum test. Correlation analysis was conducted based on count data to mine the correlation between prognosis associated miRNA model and clinicopathological factors. COX univariate analysis and multivariate analysis were applied to evaluate correlation with the results described as hazard ratio ( HR) and 95% confidence interval ( CI). HR<1 indicated the factor as a protective factor, HR>1 indicated the factor as a risk factor, and HR equal to 1 indicated no influence on survival. The Kaplan-Meier method was used to draw survival curve and calculate survival rates, and the Log-rank test was used for survival analysis. Results:(1) Survival of patients: 123 patients in the training dataset were followed up for 31-2 141 days, with a median follow-up time of 449 days. The 3- and 5-year survival rates were 16.67% and 8.06%. Forty-eight patients in the validation dataset were followed up for 41-2 182 days, with a median follow-up time of 457 days. The 3- and 5-year survival rates were 15.63% and 9.68%. There was no significant difference in the 3- or 5-year survival rates between the two groups ( χ2=0.017, 0.068, P>0.05). (2) Screening results of differentially expressed miRNAs. Results of bioinformatics analysis showed that 102 candidate differentially expressed miRNAs were selected, of which 63 were up-regulated in tumor tissues while 39 were down-regulated. (3) Construction of prognosis associated miRNA model: of the 102 candidate differentially expressed miRNAs, 5 survival associated miRNAs were selected, including miR-21, miR-125a-5p, miR-744, miR-374b, miR-664. The differential expression patterns of pancreatic cancer to adjacent tissues were up-regulation, up-regulation, down-regulation, up-regulation, and down-regulation, respectively, with the fold change of 4.00, 3.43, 3.85, 2.62, and 2.35. A prognostic expression equation constructed based on 5 survival associated miRNAs = 0.454×miR-21 expression level-0.492×miR-125a-5p expression level-0.49×miR-744 expression level-0.419×miR-374b expression level-0.036×miR-664 expression level. (4) Validation of prognosis associated miRNA model: The C-index of prognosis associated miRNA model was 0.643 and 0.642 for the training dataset and validation dataset, respectively. (5) Comparison of clinicopathological factors in pancreatic cancer patients: results of COX analysis showed that the prognosis associated miRNA model was highly related with pathological T stage and location of pancreatic cancer ( Z=45.481, χ2=10.176, P<0.05). (6) Analysis of factors for prognosis of pancreatic cancer patients: results of univariate analysis showed that pathological N stage, radiotherapy, molecular targeted therapy, score of prognosis associated miRNA model were related factors for prognosis pf pancreatic cancer patients ( HR=2.471, 0.290, 0.172, 2.001, 95% CI: 1.012-6.032, 0.101-0.833, 0.082-0.364, 1.371-2.922, P<0.05). Results of multivariate analysis showed that molecular targeted therapy was an independent protective factor for prognosis of pancreatic cancer patients ( HR=0.261, 95% CI: 0.116-0.588, P<0.05) and score of prognosis associated miRNA model≥1.16 was an independent risk factor for prognosis of pancreatic cancer patients ( HR=1.608, 95% CI: 1.091-2.369, P<0.05). (7) Comparison of prediction performance between prognosis associated miRNA model and the eighth edition TNM staging: in the training dataset, there was a significant difference in the prediction probability for 3- and 5-year survival of pancreatic cancer patients between prognosis associated miRNA model and the eighth edition TNM staging ( Z=-1.671, -1.867, P<0.05). The AUC of the prognosis associated miRNA model and the eight edition TNM staging for 3- and 5-year survival prediction was 0.797, 0.935 and 0.737 , 0.703, with the 95% CI of 0.622-0.972, 0.828-1.042 and 0.571-0.904 , 0.456-0.951. The C-index was 0.643 and 0.534. In the validation dataset, there was a significant difference in the prediction probability for 3- and 5-year survival of pancreatic cancer patients between prognosis associated miRNA model and the eighth edition TNM staging ( Z=-1.729, -1.923, P<0.05). The AUC of the prognosis associated miRNA model and the eight edition TNM staging was 0.750, 0.873 and 0.721 , 0.703, with the 95% CI of 0.553-0.948, 0.720-1.025 and 0.553-0.889, 0.456-0.950, respectively. The C-index was 0.642 and 0.544. Conclusions:A prognosis associated miRNA prediction model can be constructed based on 5 survival associated miRNAs in pancreatic cancer patients, as a complementation to current TNM staging and other clinicopathological parameters, which provides individual and accurate prediction of survival for reference in the clinical treatment.

Objective:To investigate the application value of computed tomography (CT) and magnetic resonance imaging (MRI) examination in clinical diagnosis of gallbladder tumor with perigallbladder invasion.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 80 gallbladder tumor patients with perigallbladder invasion who were admitted to 3 medical centers (21 cases in The First Affiliated Hospital of Northwest University, 42 cases in The First Affiliated Hospital of the Air Force Medical University, 17 cases in The First Affiliated Hospital of Dalian Medical University) from January 2021 to December 2022 were collec-ted. There were 45 males and 35 females, aged (56±4)years. Observation indicators: (1) CT and MRI examinations; (2) surgical conditions. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) CT and MRI examinations. Of 80 patients, cases with gallbladder cancer and gallbladder adenoma were 73 and 7, respectively. Cases with endoluminal nodular type, mass type and localized thick-walled type were 33, 39 and 8, respectively, with tumor diameter as 1.55 cm×1.35 cm×1.33 cm, 1.64 cm×1.37 cm×1.36 cm and 5.72 cm×4.07 cm×4.36 cm. Results of CT examination of endoluminal nodular type showed local nodular protrusions into the endoluminal area, and local enhancement on enhanced scanning. Results of CT examination of localized thick-walled type showed the cavity wall of lesion was locally or diffusely irregul-arly thickened, with a thickness of 1.10(range, 1.10-2.21)cm. Of 80 patients, results of CT and MRI examinations showed invasion of liver parenchyma in 68 cases, which was manifested as local mass, blurred demarcation, and abnormal protrusion. The maximum depth was (4.22±0.25)cm, (4.22±0.22)cm, (4.28±0.16)cm of cross-sectional, coronal, sagittal view in CT examination, respectively. The minimum depth was (0.22±0.10)cm, (0.25±0.08)cm, (0.24±0.12)cm. The depth of liver parenchyma invaded was (1.64±1.38)cm, (1.68±1.46)cm, (1.66±1.40)cm. Results of CT and MRI examinations showed invasion of perigallbladder, which was manifested as local invasion of the gastric antrum in 12 cases. (2) Surgical conditions. Of 80 patients, results of CT and MRI examina-tions showed that 60 patients had localized masses in the gallbladder cavity with or without infiltration of surrounding tissues. After confirming the absence of other organs and distant metastasis, cases undergoing radical resection and palliative resection were 44 and 16, respectively. Results of CT and MRI examina-tions showed that 20 patients had malignant gallbladder tumors with peri-pheral liver infiltration and multiple intrahepatic metastases with distant organ metastases, which were unresectable.Conclusion:For patients with gallbladder cancer and perigallbladder invasion, CT or MRI examina-tions can show their structural characteristics.

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).
Humans ; ST Elevation Myocardial Infarction/therapy* ; Stroke Volume ; Ventricular Remodeling ; Prospective Studies ; Microcirculation ; Ventricular Function, Left ; Myocardial Infarction/etiology* ; Treatment Outcome ; Percutaneous Coronary Intervention/adverse effects* ; Heart Failure/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic