Efficacy and safety of intracoronary pro-urokinase injection during percutaneous coronary intervention in treating ST elevation myocardial infarction patients: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Intracoronary injection of pro-urokinase (Pro-UK) during percutaneous coronary intervention (PCI) seems to be a promising treatment in improving myocardial perfusion. In this systematic review and meta-analysis, we aimed at investigating the efficacy and safety of intracoronary Pro-UK injection during PCI in ST elevation myocardial infarction (STEMI) patients. MATERIALS AND METHODS: A comprehensive literature searched on PubMed, Embase, Cochrane, Ovid-MEDLINE, Ovid-Embase, Ovid-Cochrane Databases and ClinicalTrials.gov from inception until June 1, 2022, in English only. The primary outcome was myocardial perfusion, including thrombolysis in myocardial infarction (TIMI) grades, corrected TIMI frame count (CTFC), TIMI myocardial perfusion grades (TMPG). The secondary outcomes were ST-segment resolution (STR), major adverse cardiovascular events (MACE), myocardial marker, cardiac function and hemorrhagic complications. RESULTS: We identified 5 studies (all RCTs) involving 761 participants. Under PCI procedure, compared with placebo, intracoronary Pro-UK injection may improve myocardial perfusion, including increasing the TIMI grades [odd ratio (OR) 0.46; 95% confidence interval (CI) 0.28-0.75; p = 0.002; I2 = 0%] , CTFC (OR -3.47; 95% CI [-5.60, -1.33]; p = 0.001; I2 = 0%) and TMPG (OR 0.17; 95% CI [0.06-0.44]; p = 0.0003; I2 = 0%), increase the rate of STR (OR 2.25; 95% CI [1.56-3.26]; p < 0.0001; I2 = 0%), reduce the incidence of MACE (OR 0.51; 95% CI [0.33-0.81]; p = 0.004; I2 = 0%) and reduce myocardial infarct size (CK, standardized mean difference [SMD] -0.45; 95% [CI] [-0.62, -0.28]; p < 0.00001; I2 = 10%. CK-MB, [SMD] -0.43; 95% CI [-0.68, -0.18]; p = 0.0007; I2 = 60%. cTnI, [SMD] -0.31; 95% CI [-0.46, -0.17]; p < 0.0001; I2 = 0%). Moreover, the treatment may improve the cardiac functions (LVFE, pooled mean difference [MD] 1.23; 95% CI [0.66-1.79]; p < 0.0001; I2 = 24%. LVEDd, pooled MD -0.13; 95% CI [-0.17, -0.09]; p < 0.00001; I2 = 0%). But there is no statistically significant difference between the Pro-UK group and placebo in the occurrence of hemorrhagic complications (OR 1.19; 95% CI [0.75-1.87]; p = 0.46; I2 = 0%). CONCLUSIONS: Intracoronary Pro-UK injection during PCI in STEMI patients is an effective and safe treatment to perform. The treatment may improve myocardial perfusion and rate of STR, as well as decreasing the incidence of MACE and myocardial infarct size. Importantly, the treatment may improve the cardiac functions and life quality. In the future, more multi-centered and massive sample studies are required.

[The short-term and long-term prognostic analysis in patients with chronic total occlusion acute non-ST segment elevation myocardial infarction].

Objectives: To investigate the clinical impacts of chronic total occlusion (CTO) in acute non-ST segment elevation myocardial infarction (NSTEMI) patients underwent primary percutaneous coronary intervention (PCI). Methods: A total of 2 271 acute NSTEMI patients underwent primary PCI from China Acute Myocardial Infarction Registry were enrolled in this study and divided into the CTO group and the non-CTO group according to the angiography. The primary endpoint was in-hospital mortality and mortality during a 2-year follow-up. The secondary endpoint was major adverse cardiovascular events (MACE) including revascularization, death, re-myocardial infarction, heart failure readmission, stroke and major bleeding. Results: Thirteen-point four percent of the total acute NSTEMI patients had concurrent CTO. In-hospital mortality (3.6% vs. 1.4%, P<0.01) and 2-year mortality (9.0% vs. 5.1%, P<0.01) were significantly higher in the CTO group than those in the non-CTO group, respectively. Multiple regression analyses showed that chronic obstructive pulmonary disease (HR 7.28, 95%CI 1.50-35.35, P=0.01) was an independent risk factor of in-hospital mortality, and advanced age (HR 1.04, 95%CI 1.01-1.07, P<0.01), and low levels of ejection fraction (HR 0.95, 95%CI 0.93-0.98, P<0.01) were independent risk factors of 2-year mortality. CTO (HR1.67, 95%CI 1.10-2.54, P=0.02) was an independent risk factor of revascularization, but not a risk factor of mortality. Conclusions: Although acute NSTEMI patients concurrent with CTO had higher mortality, CTO was only an independent risk factor of revascularization, but not of mortality. Advanced age and low levels of ejection fraction were independent risk factors of long-term death among acute NSTEMI patients.

[The acute and long-term outcome of patients with ST segment elevation myocardial infarction concurrent with chronic total occlusion].

Objective: To evaluate the acute and long-term outcome of patients with ST segment elevation myocardial infarction (STEMI) concurrent with chronic total occlusion (CTO) undergoing primary percutaneous coronary intervention (PCI). Methods: 11 905 STEMI patients from the China Acute Myocardial Infarction Registry were enrolled in this study and divided into CTO group and non-CTO group according to the angiography results of primary PCI. 1∶3 propensity score matching was used to match the patients between the two groups. The primary endpoint was in-hospital mortality and mortality at 1-year post PCI. The secondary endpoint was major adverse cardiovascular events (MACE) including death, re-myocardial infarction, revascularization, heart failure associated readmission, stroke and major bleeding at 1-year post PCI. Results: There were 931 CTO patients (7.8%) in this cohort (male=755 (81.1%), mean age (62.2±11.4 years)). The rest 10 974 patients were STEMI without CTO (male=8 829 (80.5%),mean age (60.0±11.8) years). After propensity score matching, 896 patients were enrolled in CTO group and 2 688 in non-CTO group. In-hospital mortality was significantly higher in the CTO group than in non-CTO group (4.2% vs. 2.4%, P=0.006). The ratio of all cause death, cardiac death, and MACE at 1-year follow up was also significantly higher in the CTO group than in non-CTO group (8.5% vs. 4.4%, P<0.001, 5.3% vs. 2.6%, P=0.001, 35.1% vs. 23.3%, P<0.001, respectively). Multiple regression analysis showed that CTO (HR=1.54, 95%CI 1.06-2.22, P=0.022), advanced age (HR=1.06, 95%CI 1.04-1.08, P<0.001), and previous heart failure history (HR=4.10, 95%CI 1.90-8.83, P<0.001) were independent risk factors of 1-year mortality. Conclusions: The in-hospital and 1-year mortality increased significantly in STEMI patients concurrent with CTO. CTO, advanced age and history of heart failure are independent risk factors of 1-year death among STEMI patients.

Twist1/2 activates MMP2 expression via binding to its promoter in colorectal cancer.

OBJECTIVE: This study aimed to characterize the effect of Twist2 on epithelial-to-mesenchymal transition (EMT) and the invasive potential of colorectal cancer (CRC) cells and to explore the mechanisms underlying the regulative effect of Twist1 and Twist2 on matrix metalloproteinase 2 (MMP2) expression in CRC. PATIENTS AND METHODS: Data mining was performed in colorectal cancer cohort (COADREAD) in the Cancer Genome Atlas (TCGA-COADREAD). CRC LoVo and HCT116 cells were used as in vitro cell models. RESULTS: CRC tumors with lymphatic invasion (N = 102) had a significantly higher expression of TWIST1 (p = 0.01) and TWIST2 (p = 0.02) than the lymphatic invasion negative cases (N = 228). TWIST2 overexpression enhanced EMT and the invasive potential of the CRC LoVo and HCT116 cells, while TWIST2 knockdown reversed the EMT process and weakened the invasive potential of the cells. TWIST1 and TWIST2 were co-upregulated with MMP2 and MMP9 in COADREAD cohort. TWIST1 or TWIST2 overexpression significantly elevated nuclear ß-catenin accumulation, which is a known signaling pathway elevating MMP2 and MMP9 expression. More importantly, we found that both Twist1 and Twist2 could transcriptionally activate MMP2 via directly binding to its promoter. However, this mechanism was not observed in the MMP9 promoter. CONCLUSIONS: TWIST1/2 is associated with lymphatic invasion in CRC. TWIST2 upregulation enhances EMT and the invasive potential of CRC cells. TWIST1/2 can enhance the Wnt/ß-catenin signaling pathway in CRC cells. In addition, Twist1/2 can bind to the MMP2 promoter and promote its transcription.

MicroRNA-143 inhibits cell growth by targeting ERK5 and MAP3K7 in breast cancer.

This study aimed to investigate the function and mechanism of microRNA-143 (miR-143) in the occurrence and development of breast cancer (BC). A total of 30 BC tissues, 30 corresponding noncancerous tissues, and 10 normal control (NC) breast tissues were obtained to detect the levels of miR-143, extracellular signal-regulated kinase 5 (ERK5) and mitogen-activated protein 3 kinase 7 (MAP3K7) using RT-qPCR, western blotting or immunohistochemistry. The correlation of miR-143 with ERK5 or MAP3K7 was evaluated using Pearson correlation analysis. MCF-7 cells were transiently transfected with miR-143 mimic, miR-143 inhibitor, miR-143 mimic/inhibitor + si-ERK5, si-MAP3K7 or si-cyclin D1. Then, cell growth was evaluated by MTT assay and the expressions of phospho-ERK5 (p-ERK5), ERK5, p-MAP3K7, MAP3K7 and cyclin D1 were detected by western blotting. Results showed that, compared with noncancerous tissues or NC breast tissues, miR-143 level was decreased, while p-ERK5, ERK5, p-MAP3K7 and MAP3K7 expressions were increased in BC tissues (all P<0.01). The miR-143 level was negatively correlated with the mRNA level of ERK5 or MAP3K7 (r=-4.231 or r=-4.280, P<0.01). In addition, up-regulated miR-143 significantly decreased the expressions of p-ERK5, ERK5, p-MAP3K7, MAP3K7 and cyclin D1 (all P<0.01), as well as cell viability in MCF-7 cells (all P<0.05) while the effect of down-regulated miR-143 was the opposite. In conclusion, both ERK5 and MAP3K7 may be the target genes of miR-143. Increased expression of miR-143 can inhibit cell growth, which may be associated with ERK5 and MAP3K7 expressions in BC.

[DOTAP liposome-mediated transfection of human adipose-derived stemcells with pIRES2-EGFP-VEGF plasmid and target gene expression].

Objective:To explore liposome-mediated transfection of human adipose-derived stem cells (hASCs) with vascular endothelial growth factor(VEGF) gene and to investigate the expression of VEGF after transfection.Method:Lipoaspirate was digested using collagenase.Cell pellet was harvested and subcultured to passage 4.Phenotype was detected with flow cytometry and multilineage differentiation was induced for the identification of hASCs.hASCs was transfected with pIRES2-EGFP-VEGF plasmid using DOTAP liposome.The intracellular expression of VEGF was detected by immunofluorescent staining and the VEGF concentration in supernatant was analyzed by ELISA.Result:1 ml lipoaspirate yielded(4.38±0.21)×105 cells.hASCs on passage 4 showed high expression of CD90(81.49%) and low expression of CD19(6.37%),CD31(14.91%),CD34(17.56%) and CD45(15.39%).GFP and VEGF were observed in transfected hASCs.The transfection efficiency was(43.69±18.53)%.Untransfected hASCs did not express GFP but low level of VEGF.The optical density of VEGF intransfected hASCs is 2.13 fold of untransfected hASCs.The VEGF concentration in supernatant of transfected hASCs significantly increased over time and exhibit statistic differences compared with untransfected hASCs(P<0.05).Conclusion:hASCs were successfully transfected with pIRES2-EGFP-VEGF plasmid using DOTAP liposome.The post-transfection expression and secretion of VEGF remarkably increased.

Remarks on the validity of Myxobolus ampullicapsulatus and Myxobolus honghuensis (Myxozoa: Myxosporea) based on SSU rDNA sequences.

In the present study, we isolated three populations of Myxobolus ampullicapsulatus from the gills of crucian carp, Carassius auratus auratus, two from Yongchuan, Chongqing area and one from Poyang Lake, Jiangxi area, China, sequenced their complete small subunit ribosome RNA gene, analyzed their genetic distance and gene similarity, and explored their relationship based on Bayesian inference and maximum likelihood analyses of their small subunit ribosomal DNA. The results combined with their morphological characteristics suggest that M. ampullicapsulatus infecting the gills and pharynx of allogynogenetic gibel carp, Carassius auratus gibelio, should be Myxobolus honghuensis. This study highlights the importance of DNA sequence comparisons for distinguishing Myxobolus species and indicates that the intra-species identification for the two Myxobolus species mentioned in the present research should be less than ten variation sites. In morphology, M. honghuensis Liu et al. (2012) parasitic on the gills of C. auratus auratus (goldfish) was collected from Chongqing area, and its mature spore was 16.5-19.5 × 8.5-10.0 µm in size, polar capsule was 7.0-10.0 × 2.5-4.0 µm in size, and polar filament had 9-10 coils. M. honghuensis Liu et al. (2012) isolated from the pharynx of C. auratus gibelio was sampled in Hubei area, and its mature spore was 15.1-19.5 × 9.0-11.3 µm in size, polar capsule was 7.9-8.1 × 3.0-4.5 µm in size, and polar filament had 7-8 coils.

[Analysis of 65 cases of abruptio placenta].

From Jan 1, 1971 to Dec 12, 1990, 65 cases of abruptio placenta were admitted to our hospital. The incidence was 0.19%. Among them, thirty were complicated by pregnancy induced hypertension (46.2%). The perinatal fetal mortality was 19.7%; perinatal death occurred mostly in the premature group. All babies survived except two abnormalities. Cesarean section rate was 32.3%. All postpartum hemorrhage 29.2%. Couvelaire uterus 6.2%, were cured by conservative treatment. There was neither stillbirth nor newborn death in the thirty three cases treated expectant, but a newborn asphyxia rate of 6.1% and a cesarean section rate of 15.1%. Analysis showed that abruptio placentae should be suspected in cases with abnormal fetal heart rate of unknown cause accompanying signs of labor, premature labor of unknown cause, uterine tongue, ultrasonically visualized liquid from dark area behind the placenta, besides classical signs of abdominal pain and vaginal bleeding. Expectant treatment is appropriate if gestational age is small and no acute symptoms exists so as to minimize the perinatal mortality and cesarean section rate.