Prognostic Value of GRACE Risk Score Combined With Systemic Immune-Inflammation Index in Patients With ST-Segment Elevation Myocardial Infarction After Percutaneous Coronary Intervention.

The Global Registry of Acute Coronary Events (GRACE) score and the systemic immune-inflammation index (SII) were used independently to predict adverse outcomes in patients with ST-elevation myocardial infarction (STEMI). In this study, 1041 patients with STEMI were divided into 4 groups based on GRACE scores and optimal cutoff values for SII. SII was positively correlated with GRACE score (r = 0.164; P < .001). SII (HR, hazard ratio: 2.051; 95%CI: 1.249-3.368; P = .005) and GRACE score (HR: 7.625; 95%CI: 3.692-15.746; P < .001) were independent risk predictors of short-term major adverse cardiovascular events (MACEs). Taking the low SII+low GRACE group as the reference group, the short-term MACE HR of the high SII+high GRACE group was 40.470 (95%CI: 5.547-295.253). Comparing the area under the curve, the combined use of SII and GRACE scores can significantly improve the prediction efficiency of short-term MACE compared with the single use of SII and GRACE scores. In conclusion, SII may be positively correlated with GRACE score, and the combination of the two accurately predicted the occurrence of short-term MACE in STEMI patients after percutaneous coronary intervention (PCI).

The Relationship Between Microbial Community and Breast Cancer.

Breast cancer (BC) is the most common cancer in women and the leading cause of cancer-related deaths in women worldwide. Recent research studies have shown that the intestinal flora is related to the occurrence and progression of BC. Notably, some evidence identifies a unique microbial community in breast tissue, a site previously thought to be sterile. In addition, breast tumors have their own specific microbial community, distinct from normal mammary gland tissue, and all of them may result from intestinal flora. Some microbial community in breast tissue may lead to the occurrence and development of BC. This review focuses on the relationship between the microbial community and breast cancer, which will lay a solid theoretical foundation for further understanding the local microenvironment of BC and developing effective targeted therapeutic drugs.

The Signaling Pathways Associated With Breast Cancer Bone Metastasis.

Background: Breast cancer (BC) is now the leading cause of cancer in women, and bone is the primary site of distant BC metastasis. BC bone metastasis seriously affects the quality of life of patients and increases the mortality rate. However, the mechanism of BC bone metastasis is not fully understood. Main Body: Paget's "seed and soil" hypothesis led experts to explore the relationship between surface markers and receptors in breast tumors and various growth factors in bone. The relevant breast tumor markers serve as "seeds", and the bone microenvironment that is suitable for the survival of the tumor serves as the "soil". These factors interact to make up an entire system and form feedback pathways that accelerate the production of various cytokines, attracting BC cells to migrate to bone tissue, which worsens the development of BC and seriously affects the prognosis of patients. This process is a vicious cycle. At present, there are seven major signaling pathways involved in BC bone metastasis: the OPG/RANK/RANKL signaling pathway, TGF-ß signaling pathway, IGF system, PI3K-AKT-mTOR signaling pathway, Wnt signaling pathway and Hippo signaling pathway. In addition, FGF-FGFR signaling pathway, androgen-AR/LSD1-target gene pathway, Notch signaling pathway, JAK-STAT signaling pathway and CaN/NFATC1 signaling pathway also seem to be associated with BC bone metastasis. Conclusion: This review focuses on the signaling pathways related to BC bone metastasis and explores the interactions among these pathways, which will lay a solid theoretical foundation for further understanding the mechanism of BC bone metastasis and developing effective targeted therapeutic drugs.

Association between γδ T cells and clinicopathological features of breast cancer.

BACKGROUND: The roles of γδ T cells in patients with breast cancer (BC) have not been fully clarified, although the efficacy of gamma delta (γδ) T cells, which combine both innate and adaptive potential have extraordinary properties, such as recognizing tumor cells without the need for major histocompatibility complex (MHC) antigen presentation, as well as killing a broad range of tumor cells through their strong cytotoxic and pro-inflammatory activity, has been suggested in the majority of patients with some certain cancers. PURPOSE: To understand and dissect the association between γδ T cells and the clinical pathology of BC by measuring and analyzing the γδ T cell populations in the patients with BC. METHODS: On the one hand, γδ T cells were measured and analyzed by extracting from peripheral blood mononuclear cells (PBMC) of patients with BC. On the other hand, γδ T cells were measured and analyzed by performing enzymatic digestion in primary BC tissues, cancer adjacent tissues, and distant normal breast tissues from patients with different stages of cancer progression. In addition, patients with breast benign tumors and healthy volunteers were also collected as controls for this study. RESULTS: The proportion of γδ T cells in PBMC was significantly correlated with tumor histological grade, ER status, the proportional value of Ki-67, and lymph node (LN) metastasis. The decrease and exhaustion of γδ T cells were a general feature in the PBMC of BC patients. In addition, the primary BC tissue infiltration of γδ T cells was significantly associated with tumor histological grade, ER status, the proportional value of Ki-67, and LN metastasis. CONCLUSION: These findings suggest that γδ T cell populations are crucial for understanding the clinicopathological features of patients with BC, and may serve as a valuable and independent biomarker, as well as a potential therapeutic target for human BC.

Successful optical coherence tomography-guided treatment in a 19-year-old patient with ST-segment elevation myocardial infarction caused by plaque erosion.

ST-segment elevation myocardial infarction is a type of coronary atherosclerotic heart disease, and its pathophysiological mechanism is formation of lipid plaques. We report a 19-year-old patient with ST-segment elevation myocardial infarction caused by plaque erosion, but he did not have any common traditional risk factors of lipid plaques. His treatment was guided by optical coherence tomography. He received successful treatment and had a good prognosis. Optical coherence tomography can be used to help understand the pathogenesis of myocardial infarction and visualize the real lumen.

Thrombus aspiration during primary percutaneous coronary intervention improved outcome in patients with STEMI and a large thrombus burden.

BACKGROUND: The benefit of thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) to patients with ST-segment elevation myocardial infarction (STEMI) remains controversial. This study aimed to assess TA's impact on the outcome and prognosis for patients with STEMI and a large thrombus burden during PPCI. METHODS: This retrospective study evaluated consecutive patients with STEMI and a large thrombus burden (thrombolysis in myocardial infraction [TIMI] thrombus grade ≥4) who underwent conventional PPCI (n = 126) or PPCI + TA (n = 208) between February 2017 and January 2019. The procedure outcome and clinical prognosis were compared. RESULTS: Postprocedural vessel diameter was larger, and corrected TIMI frame count (cTFC) was lower in the PPCI + TA compared with the PPCI group. The proportion of postprocedural TIMI 3 flow was 83.3% in the PPC group and 94.2% in the PPCI+TA group. During the 12-month follow-up, no significant differences existed in the incidence of cardiac death, reinfarction, stent thrombosis, target vessel revascularization, or stroke. CONCLUSION: Application of TA in patients with STEMI and a large thrombus burden during PPCI may improve the procedural outcome, but it showed no benefit on the clinical prognosis in the 12-month follow-up. Longer follow-up studies are needed to confirm TA's clinical implications in patients with STEMI.

Successful ablation of a left anterior accessory pathway from the left coronary sinus of Valsalva near the aortic-mitral continuity.

Catheter ablation of accessory pathways can be challenging depending on the location of these pathways, and accessory pathways are rare through the aortic cusps. We report a patient who underwent radiofrequency catheter ablation for manifestation of a left anterior accessory pathway from the left coronary sinus of Valsalva near the aortic-mitral continuity. Anterior accessory pathways can be safely and effectively ablated from the aortic cusps with favorable long-term outcomes.

The potential role and status of IL-17 family cytokines in breast cancer.

Breast cancer (BC) is currently the most common malignant tumor of women in the world. At present, the development of BC is accelerating and showing a younger trend, which may be due to the known and/or unknown risk factors (RFs) for BC are increasing. It has been reported that inflammatory factors promote the occurrence and development of BC. No doubt chronic inflammation could trigger a series of molecular events, which will lead to the malignant transformation of differentiated cells, inhibition of anti-tumor immunity, and finally, lead to the occurrence and metastasis of tumors. With the deepening of research, it has been found that pro-inflammatory cytokine-interleukin-17 (IL-17) is closely related to BC. It not only plays an important role in promoting tumor proliferation, invasion and metastasis, but also has a significant correlation with poor prognosis. Recently, it was reported that IL-17 is closely related to programmed death ligand 1 (PD-L1) in BC. Therefore, starting with the role of IL-17 family cytokines in BC, this paper briefly discusses the potential role and status of IL-17 and seeks to contribute to the development of targeted drugs for BC-related treatments and to the identification of prediction factors for the early detection and prognosis prediction of BC for laying a solid theoretical foundation.

Sacubitril/valsartan inhibits ox­LDL­induced MALAT1 expression, inflammation and apoptosis by suppressing the TLR4/NF­κB signaling pathway in HUVECs.

The therapeutic effect of sacubitril/valsartan (S/V) on heart failure has been confirmed, while its role in atherosclerosis remains largely unexplored. The present study aimed to investigate the effects of S/V on the expression of metastasis­associated lung adenocarcinoma transcript 1 (MALAT1), inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs) induced by oxidized low­density lipoprotein (ox­LDL) and to elucidate its possible mechanism. Cell Counting Kit­8 assay was used to detect cell viability. Reverse transcription­quantitative PCR was performed to detect the MALAT1 expression. ELISA was performed to detect the levels of IL­1ß, IL­6 and TNF­α. Flow cytometry was conducted to detect the apoptotic rate of cells. A nitric oxide (NO) detection kit was used to determine the concentration of NO. Western blotting analysis was performed to determine the levels of intercellular cell adhesion molecule (ICAM)­1, vascular cell adhesion molecule (VCAM)­1, endothelin­1, caspase­3, Bax, Bcl­2, Toll­like receptor 4 (TLR4), p65 and p­p65. Compared with the ox­LDL group, S/V treatment significantly increased the cell viability, NO concentration and Bcl­2 expression, decreased the levels of IL­1ß, IL­6 and TNF­α and reduced the expressions of MALAT1, ICAM­1, VCAM­1, cleaved­caspase­3, Bax, TLR4 and p­p65. Overall, the findings suggested that S/V could downregulate the expression of MALAT1, inhibit inflammation and apoptosis and improve endothelial function in ox­LDL­induced HUVECs via inactivating the TLR4/NF­κB signaling pathway. Therefore, S/V might be utilized as a promising therapeutic strategy for the prevention and treatment of atherosclerosis.

miR-362-3p Targets Orosomucoid 1 to Promote Cell Proliferation, Restrain Cell Apoptosis and Thereby Mitigate Hypoxia/Reoxygenation-Induced Cardiomyocytes Injury.

This study aimed to investigate the mechanism of how miR-362-3p/orosomucoid 1 (ORM1) involved in hypoxia/reoxygenation (H/R)-induced cardiomyocytes injury. Based on data obtained from Gene Expression Omnibus (GEO) database, we revealed that ORM1 was highly expressed and positively correlated with the expression of inflammatory factors (MAPK1, MAPK3, IL1B and CASP9). miR-362-3p was identified as an upstream regulatory miRNA of ORM1 and negatively modulated the mRNA and protein expression levels of ORM1 in H/R-injured cardiomyocytes. Moreover, we found that miR-362-3p was downregulated in cardiomyocytes injured by H/R. The promoting influence of miR-362-3p mimic on the proliferation and the inhibitory effect of miR-362-3p mimic on the apoptosis of H/R-stimulated cardiomyocytes were eliminated by overexpression of ORM1. Furthermore, miR-362-3p affected the expression of MAPK1, MAPK3, IL1B and CASP9 in H/R-injured cardiomyocytes through targeting ORM1. Our outcomes illustrated that miR-362-3p exhibited a protective influence on H/R-induced cardiomyocytes through targeting ORM1.

Experience of ST Segment Elevation Myocardial Infarction Management During COVID-19 Pandemic From the Mainland of China.

BACKGROUND: The pandemic of COVID-19 has created a crisis in healthcare systems across the globe. This situation would affect the diagnosis and treatment of patients with STEMI. The outbreak was under improved control in the mainland of China. We here describe the impact of this pandemic on STEMI patient's management. METHODS: Information of STEMI patient management was collected from the CPC data reporting platform. We compared these with data of patients from the same period in 2018 and 2019. Also we made an analysis of those characteristics in each month in 2020. RESULTS: There was 51.4% decrease of STEMI patients admitted to hospital during the peak period of COVID-19 epidemic. The ratio of no reperfusion of STEMI patients is more than 10% higher in 2020 than 2018, 2019. The percentage of STEMI patients received fibrinolysis in 2020 was 2 to 3 times higher than that in 2018, 2019, while the volume of PPCI dropped by more than half. The mortality rate of whole cohort and perioperative was the highest in February 2020. CONCLUSIONS: COVID-19 pandemic dramatically reduced the number of STEMI patients attending hospital and delay the time to treatment and consequently, a higher in-hospital mortality. The benefits of thrombolysis during the pandemic remain to be proven.

LncRNA A2M-AS1 lessens the injury of cardiomyocytes caused by hypoxia and reoxygenation via regulating IL1R2.

BACKGROUND: Myocardial ischemia and reperfusion injury (MI/RI) is a complex pathophysiological process, which can lead to severe myocardial injury. The long noncoding RNA alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) has been revealed to be abnormally expressed in MI, However, its function in MI and the potential mechanism are still unclear. OBJECTIVE: To evaluate the functional role of A2M-AS1 in hypoxia/reoxygenation (H/R)-induced neonatal cardiomyocytes and its potential molecular mechanism. METHODS: Dataset GSE66360 was obtained from GEO database for analyzing the RNA expression of A2M-AS1 and interleukin 1 receptor type 2 (IL1R2). KEGG pathway enrichment analysis of the genes that co-expressed with A2M-AS1 was performed. Human neonatal cardiomyocytes were subjected to H/R to construct in vitro models. QRT-PCR and Western blot were adopted to test the levels of mRNA and protein. The viability and apoptosis of cardiomyocytes were tested by CCK-8 and flow cytometry assays, respectively. RESULTS: The expression of A2M-AS1 was notably downregulated in H/R-treated cardiomyocytes. Overexpression of A2M-AS1 can notably enhance the cell viability of H/R-damaged cardiomyocytes, whereas knockdown of A2M-AS1 showed the opposite outcomes. Besides, a negative correlation was showed between A2M-AS1 and IL1R2 expression. In H/R-treated cardiomyocytes, overexpression of IL1R2 weakened the promoting proliferation and anti-apoptosis effects caused by overexpressing A2M-AS1, however, IL1R2-knockdown abolished the anti-proliferation and pro-apoptosis effects caused by silencing A2M-AS1. CONCLUSION: This study demonstrates the potential regulatory role of A2M-AS1/ IL1R2 axis in cardiomyocytes suffered from H/R, and provides insight into the protection of MI/RI.

Cardiac contractility modulation attenuates structural and electrical remodeling in a chronic heart failure rabbit model.

BACKGROUND: Cardiac contractility modulation (CCM) is non-excitatory electrical stimulation for improving cardiac function. This study aimed to evaluate the effects of CCM on structural and electrical remodeling in a rabbit model of chronic heart failure (CHF). METHODS: Thirty rabbits were randomly divided into the sham, CHF, and CCM groups. The CHF model was induced 12 weeks after trans-aortic constriction by pressure unloading and CCM was delivered to the myocardium for 4 weeks. Corrected QT intervals, the ventricular effective refractory period, and inducibility of ventricular tachycardia were measured by an electrophysiological examination. Connective tissue growth factor, galectin-3, Kv4.3, KCNQ1, KCNH2, and connexin 43 protein levels were measured by western blotting. RESULTS: The CHF group had a significantly prolonged corrected QT interval and ventricular effective refractory period, and increased inducibility of ventricular tachycardia. Prominent myocardial fibrosis and increased hydroxyproline content were observed in the CHF group, but these were suppressed in the CCM group. Kv4.3, KCNQ1, KCNH2, and connexin 43 protein levels were significantly lower in the CHF group, but treatment with CCM partially restored their levels. CONCLUSIONS: CCM attenuates myocardial structural and electrical remodeling during CHF. These findings provide evidence for clinical use of CCM in treating CHF.

Disentangling the effects of driving forces on soil bacterial and fungal communities under shrub encroachment on the Guizhou Plateau of China.

Global shrub encroachment (SE) affects the structure and function of grassland ecosystem. The effects of SE on plant and soil abiotic properties have been well studied; however, little is known about the extent to which driving forces structure soil microbes under SE, especially in subalpine regions of the Guizhou Plateau of China, which is undergoing progressive SE. We investigated the plant factors (viz, plant diversity and relative shrub cover), soil physicochemical properties, enzymatic activities, and microbial communities, quantified microbial element limitations under three encroachment stages, and disentangled the effects sizes of the factors that structure the diversity and composition of soil microbial communities. Redundancy analysis showed that soil factors made a greater contribution than plant factors to shaping the diversity and composition of the soil bacterial community, soil chemical factors made a greater contribution than physical factors both to structuring the diversity and composition of the soil bacterial community and to structuring the composition of the soil fungal community; and soil nutrient stoichiometry made a greater contribution than soil nutrient content to shaping soil bacterial community's diversity and fungal community's composition. In contrast, soil nutrient content made a greater contribution than soil nutrient stoichiometry to shaping the soil bacterial community's composition. The decrease in bacterial community's diversity observed under SE was attributable to increases in the carbon and nitrogen limitations consequent to SE, and the nitrogen limitation had a greater contribution to the soil bacterial community's diversity and composition than did the carbon limitation. These findings provide updated knowledge of the driving forces shaping the diversity and composition of soil microbial communities, which could be crucial for improving microbial prediction models and revealing the element cycling that occurs in SE biomes.

Effects of atorvastatin on atrial remodeling in a rabbit model of atrial fibrillation produced by rapid atrial pacing.

BACKGROUND: Accumulating evidence suggests that myeloperoxidase (MPO) is involved in atrial remodeling of atrial fibrillation (AF). Statins could reduce the MPO levels in patients with cardiovascular diseases. This study evaluated the effects of atorvastatin on MPO level and atrial remodeling in a rabbit model of pacing-induced AF. METHODS: Eighteen rabbits were randomly divided into sham, control and atorvastatin groups. Rabbits in the control and atorvastatin groups were subjected to rapid atrial pacing (RAP) at 600 bpm for 3 weeks, and treated with placebo or atorvastatin (2.5 mg/kg/d), respectively. Rabbits in the sham group did not receive RAP. After 3 weeks of pacing, atrial structural and functional changes were assessed by echocardiography, atrial effective refractory period (AERP) and AF inducibility were measured by atrial electrophysiological examination, and histological changes were evaluated by Masson trichrome-staining. The L-type calcium channel α1c (Cav1.2), collagen I and III, MPO, matrix metalloproteinase (MMP)-2 and MMP-9 were analyzed by real time polymerase chain reaction and/or western blot. RESULTS: All rabbits were found to have maintained sinus rhythm after 3 weeks of RAP. Atrial burst stimulation induced sustained AF (>30 min) in 5, 4, and no rabbits in the control, atorvastatin, and sham groups, respectively. The AERP shortened and Cav1.2 mRNA level decreased in the control group, but these changes were suppressed in the atorvastatin group. Obvious left atrial enlargement and dysfunction was found in both control and atorvastatin groups. Compared with the control group, these echocardiograhic indices of left atrium did not differ in the atorvastatin group. Prominent atrial fibrosis and increased levels of collagen I and III were observed in the control group but not in the atorvastatin group. The mRNA and protein levels of MPO, MMP-2 and MMP-9 significantly increased in the control group, but these changes were prevented in the atorvastatin group. CONCLUSION: Treatment with atorvastatin prevented atrial remodeling in a rabbit model of RAP-induced AF. The reduction of levels of atrial MPO, MMP-2 and MMP-9 may contribute to the prevention of atorvastatin on atrial remodeling.

[Impact of statin therapy on recurrence of persistent atrial fibrillation after electrical cardioversion: a meta-analysis].

OBJECTIVE: To evaluate the impact of statin therapy on the recurrence rate in patients with persistent atrial fibrillation (AF) after electrical cardioversion. METHODS: PubMed, EMBbase, Cochrane central register of controlled trials were searched up to February 2015 to identify randomized controlled trials, which reported the effect of statin therapy on AF recurrence after electrical cardioversion. The data were analyzed by RevMan 5.3 and Stata 12.0 software. RESULTS: Six trials with 572 patients were included. The result showed that statin therapy had no effect on the recurrence rate in patients with persistent AF after electrical cardioversion (OR=0.60, 95%CI: 0.32-1.11, P>0.05) compared with controls. Four out of the six trials investigated the effect of atorvastatin on the recurrence rate of AF after electrical cardioversion, subgroup analysis of these trials showed that compared with controls, atorvastatin had no effect on the recurrence of AF after electrical cardioversion (OR=0.59, 95%CI: 0.25-1.39, P>0.05). Three out of the six trials had high quality (Jadad score≥3), subgroup analysis of these trials also showed that statins did not affect the recurrence rate of AF after electrical cardioversion (OR=0.76, 95%CI: 0.49-1.16, P>0.05). CONCLUSION: This analysis suggested that statin therapy had no effect on the recurrence rate in patients with persistent AF after electrical cardioversion.

[An in vitro evaluation of the effect of carboxymethyl chitosan and its composites against Enterococcus faecalis in the root canal].

PURPOSE: To evaluate the bacteriostasis effect of carboxymethyl chitosan and its composites on intracanal E. faecalis. METHODS: The pattern of E. faecalis infecting root canal was established, and then divided into 4 groups(A, B, C and D).They were filled with 2% chlorhexidine solution, 140 mg/mL mixture of carboxymethyl chitosan and chlorhexidine solution, 5 mg/mL carboxymethyl chitosan solution and calcium hydroxide paste respectively and incubated for 7 days. Samples obtained before and after the intracanal medication were plated onto BHI media to determine the colony-forming units (CFU/mL) after 48 hours. The data were analysed using SPSS 13.0 software package. RESULTS: Before intracanal medication, the variance of bacterial counts were not significantly different (P>0.05). After medication, the four groups showed significant difference in bacterial counts immediately(P<0.05).The antimicrobial effects of A and B group were better than group C and D. CONCLUSIONS: The antibiotic activity of 2% chlorhexidine solution and 140 mg/L mixture of carboxymethyl chitosan and chlorhexidine solution to E.faecalis were better. Supported by Key Science and Technology Project of Liaoning Province(2010225001).

[Study of the effect of chitosan and its composites on proliferation and differentiation of mouse osteoblasts].

PURPOSE: A mouse osteoblast cell line, MC3T3-E1, was cultivated in the medium that contained chitosan, type I collagen and recombinant human bone morphogenetic protein-2 in vitro to evaluate the effect of chitosan and its composites on proliferation and differentiation of mouse osteoblasts. METHODS: This study was categorized into 4 groups based on the medium used. Group A: α-MEM medium; group B: CS, type I collagen and α-MEM medium; group C: CS, type I collagen, rhBMP-2 and α-MEM medium. α-MEM medium containing 1%FBS was used in the control group. Cells of each group were cultivated for 1,3,5 and 7 days. The optical density (OD) value at each time point was evaluated with MTT assay and growth curve was drawn to observe the proliferation of osteoblasts. Differentiation of osteoblasts was determined with alkaline phosphatase (ALP) activity assay, alkaline phosphatase staining and alizarin red staining. Alkaline phosphatase activity of each group was measured at day 1, 3, 5 and 7 days. After 7 days of culture, the cells were stained with alkaline phosphatase, and at day 14, the mineralized nodules were stained with alizarin red. Statistical analysis was performed using SPSS13.0 software package. RESULTS: The MTT assay results showed that the OD value was maximal when osteoblasts were cultured in group C. The difference were statistically significant between group C and others (P<0.05). The ALP activity showed that the result of group C was significantly higher than other groups. The increase of ALP activity was significant between group C and control group (P<0.05). However, no significant difference was found between group C and group B (P>0.05). Compared with the control group, group C had more calcium nodules and blue particles than others. CONCLUSIONS: The incorporation of type I collagen and bone morphogenetic protein-2 into chitosan can promote MC3T3-E1 cell proliferation and differentiation better. Supported by Major Science and Technology Project of Liaoning Province (2010225001).