Quantitative Detection of Multiple Cardiovascular Biomarkers by an Antibody Microarray-Based Metal-Enhanced Fluorescence Assay.

Accurate detection of multiple cardiovascular biomarkers is crucial for the timely screening of acute coronary syndrome (ACS) and differential diagnosis from acute aortic syndrome (AAS). Herein, an antibody microarray-based metal-enhanced fluorescence assay (AMMEFA) has been developed to quantitatively detect 7 cardiovascular biomarkers through the formation of a sandwich immunoassay on the poly(glycidyl methacrylate-co-2-hydroxyethyl methacrylate)-decorated GNR-modified slide (GNR@P(GMA-HEMA) slide). The AMMEFA exhibits high specificity and sensitivity, the linear ranges span 5 orders of magnitude, and the limits of detection (LODs) of cardiac troponin I (cTnI), heart-type fatty acid binding protein (H-FABP), C-reactive protein (CRP), copeptin, myoglobin, D-Dimer, and N-terminal pro-brain natriuretic peptide (NT-proBNP) reach 0.07, 0.2, 65.7, 0.6, 0.2, 8.3, and 0.3 pg mL-1, respectively. To demonstrate its practicability, the AMMEFA has been applied to quantitatively analyze 7 cardiovascular biomarkers in 140 clinical plasma samples. In addition, the expression levels of cardiovascular biomarkers were analyzed by the least absolute shrinkage and selector operator (LASSO) regression, and the area under receiver operator characteristic curves (AUCs) of healthy donors (HDs), ACS patients, and AAS patients are 0.99, 0.98, and 0.97, respectively.

Lp-PLA2 (Lipoprotein-Associated Phospholipase A2) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits.

BACKGROUND: Elevated plasma Lp-PLA2 (lipoprotein-associated phospholipase A2) activity is closely associated with an increased risk of cardiovascular events. However, whether and how Lp-PLA2 is directly involved in the pathogenesis of atherosclerosis is still unclear. To examine the hypothesis that Lp-PLA2 could be a potential preventative target of atherosclerosis, we generated Lp-PLA2 knockout rabbits and investigated the pathophysiological functions of Lp-PLA2. METHODS: Lp-PLA2 knockout rabbits were generated using CRISPR/Cas9 system to assess the role of Lp-PLA2 in plasma lipids regulation and identify its underlying molecular mechanisms. Homozygous knockout rabbits along with wild-type rabbits were fed a cholesterol-rich diet for up to 14 weeks and their atherosclerotic lesions were compared. Moreover, the effects of Lp-PLA2 deficiency on the key cellular behaviors in atherosclerosis were assessed in vitro. RESULTS: When rabbits were fed a standard diet, Lp-PLA2 deficiency led to a significant reduction in plasma lipids. The decreased protein levels of SREBP2 (sterol regulatory element-binding protein 2) and HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) in livers of homozygous knockout rabbits indicated that the cholesterol biosynthetic pathway was impaired with Lp-PLA2 deficiency. In vitro experiments further demonstrated that intracellular Lp-PLA2 efficiently enhanced SREBP2-related cholesterol biosynthesis signaling independently of INSIGs (insulin-induced genes). When fed a cholesterol-rich diet, homozygous knockout rabbits exhibited consistently lower level of hypercholesterolemia, and their aortic atherosclerosis lesions were significantly reduced by 60.2% compared with those of wild-type rabbits. The lesions of homozygous knockout rabbits were characterized by reduced macrophages and the expression of inflammatory cytokines. Macrophages of homozygous knockout rabbits were insensitive to M1 polarization and showed reduced DiI-labeled lipoprotein uptake capacity compared with wild-type macrophages. Lp-PLA2 deficiency also inhibited the adhesion between monocytes and endothelial cells. CONCLUSIONS: These results demonstrate that Lp-PLA2 plays a causal role in regulating blood lipid homeostasis and Lp-PLA2 deficiency protects against dietary cholesterol-induced atherosclerosis in rabbits. Lp-PLA2 could be a potential target for the prevention of atherosclerosis.

Rare left-sided accessory pathway successfully ablated with atrial insertion site at the left-side fossa ovalis.

INTRODUCTION: Left-sided accessory pathway (AP) with atrial insertion away from the annulus is an atypical variation. Conventional mapping and ablation performed along mitral annulus (MA) is usually ineffective. METHODS: A 14-year-old girl without structural heart disease presented with recurrent episodes of sudden onset palpitations and electrocardiogram (ECG) showed a narrow QRS complex tachycardia. RESULTS: Electrophysiology study (EPS) was done and anterograde atrioventricular reentrant tachycardia (AVRT) with AP was diagnosed. Conventional mapping and ablation performed along TA and MA was failed. 3D-activation mapping found the retrograde atrial insertion site of AP on the left atrium fossa ovalis (FO), and AP was successfully abolished by radiofrequency ablation at that site. CONCLUSION: As reported, this patient is the first report of ablating a left-sided AP with retrograde atrial insertion on the left atrium FO.

Cardio-Oncology: Mechanisms, Drug Combinations, and Reverse Cardio-Oncology.

Chemotherapy, radiotherapy, targeted therapy, and immunotherapy have brought hope to cancer patients. With the prolongation of survival of cancer patients and increased clinical experience, cancer-therapy-induced cardiovascular toxicity has attracted attention. The adverse effects of cancer therapy that can lead to life-threatening or induce long-term morbidity require rational approaches to prevention and treatment, which requires deeper understanding of the molecular biology underpinning the disease. In addition to the drugs used widely for cardio-protection, traditional Chinese medicine (TCM) formulations are also efficacious and can be expected to achieve "personalized treatment" from multiple perspectives. Moreover, the increased prevalence of cancer in patients with cardiovascular disease has spurred the development of "reverse cardio-oncology", which underscores the urgency of collaboration between cardiologists and oncologists. This review summarizes the mechanisms by which cancer therapy induces cardiovascular toxicity, the combination of antineoplastic and cardioprotective drugs, and recent advances in reverse cardio-oncology.

Comparison of one-month versus twelve-month dual antiplatelet therapy after implantation of drug-eluting stents guided by either intravascular ultrasound or angiography in patients with acute coronary syndrome: rationale and design of prospective, multicenter, randomized, controlled IVUS-ACS and ULTIMATE-DAPT trial.

BACKGROUND: Current guidelines recommend administering dual antiplatelet therapy (DAPT) for 12 months to patients with acute coronary syndromes (ACS) and without contraindications after drug-eluting stent (DES) implantation. A recent study reported that 3 months of DAPT followed by ticagrelor monotherapy is effective and safe in ACS patients undergoing DES implantation compared with the standard duration of DAPT. However, it is unclear whether antiplatelet monotherapy with ticagrelor alone versus ticagrelor plus aspirin reduces the incidence of clinically relevant bleeding without increasing the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in ACS patients undergoing percutaneous coronary intervention (PCI) with DES implantation guided by either intravascular ultrasound (IVUS) or angiography who have completed a 1-month course of DAPT with aspirin plus ticagrelor. METHODS: The IVUS-ACS and ULTIMATE-DAPT is a prospective, multicenter, randomized, controlled trial designed to determine (1) whether IVUS-guided versus angiography-guided DES implantation in patients with ACS reduces the risk of target vessel failure (TVF) at 12 months and (2) whether ticagrelor alone versus ticagrelor plus aspirin reduces the risk of clinically relevant bleeding without increasing the risk of MACCE 1-12 months after the index PCI in ACS patients undergoing DES implantation guided by either IVUS or angiography. This study will enroll 3486 ACS patients eligible for DES implantation, as confirmed by angiographic studies. The patients who meet the inclusion criteria and none of the exclusion criteria will be randomly assigned in a 1:1 fashion to the IVUS- or angiography-guided group (first randomization). All enrolled patients will complete a 1-month course of DAPT with aspirin plus ticagrelor after the index PCI. Patients with no MACCEs or major bleeding (≥Bleeding Academic Research Consortium (BARC) 3b) within 30 days will be randomized in a 1:1 fashion to either the ticagrelor plus matching placebo (SAPT)group or ticagrelor plus aspirin (DAPT)group for an additional 11 months (second randomization). The primary endpoint of the IVUS-ACS trial is TVF at 12 months, including cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target vessel revascularization (CD-TVR). The primary superiority endpoint of the ULTIMATE-DAPT trial is clinically relevant bleeding, defined as BARC Types 2, 3, or 5 bleeding, and the primary non-inferiority endpoint of the ULTIMATE-DAPT trial is MACCE, defined as cardiac death, myocardial infarction, ischemic stroke, CD-TVR, or definite stent thrombosis occurring 1-12 months in the second randomized population. CONCLUSION: The IVUS-ACS and ULTIMATE-DAPT trial is designed to test the efficacy and safety of 2 different antiplatelet strategies in ACS patients undergoing PCI with DES implantation guided by either IVUS or angiography. This study will provide novel insights into the optimal DAPT duration in ACS patients undergoing PCI and provide evidence on the clinical benefits of IVUS-guided PCI in ACS patients.

Comparison of intravascular ultrasound-guided with angiography-guided double kissing crush stenting for patients with complex coronary bifurcation lesions: Rationale and design of a prospective, randomized, and multicenter DKCRUSH VIII trial.

BACKGROUND: Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. TRIAL DESIGN: DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. CONCLUSIONS: DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.

In-stent restenosis and longitudinal stent deformation: a case report.

BACKGROUND: Longitudinal stent deformation (LSD) is an infrequent complication of percutaneous coronary intervention (PCI), and it may lead to catastrophic clinical outcomes. However, reports of cardiac adverse events associated with LSD are rare. CASE PRESENTATION: A 55-year-old man with chest pain was treated for a severe left anterior descending branch (LAD)-diagonal 1 (D1) bifurcation lesion by PCI with two stents in the proximal LAD. LSD occurred during the withdrawal of the trapped D1 wire. High-pressure balloon dilatation was performed in the deformed stent, and the end-angiographic appearance was acceptable, but no additional corrective measures were implemented. Ten months later, the patient represented with acute coronary syndrome. Severe in-stent restenosis (ISR) had suboccluded the proximal LAD, and optical coherence tomography (OCT) visualized multilayered stent struts protruding into the lumen at the compressed segment of the stent. Following complete apposition with balloon dilation, a drug-coated balloon (DCB) was used to avoid an additional permanent metallic layer. He remained angina free, and the angiographic result demonstrated no residual stenosis at the six-month follow-up. To our knowledge, this case demonstrates the first report of ISR triggered by LSD in patients treated with DCBs under the guidance of OCT. CONCLUSIONS: The current report underscores the importance of awareness of LSD, and OCT seems to be the preferred modality to confirm complete apposition. If left without performing additional corrective measures, LSD may be associated with a risk of ISR. Complete apposition with balloon dilation followed by a DCB is a feasible treatment option.

Revisiting right anterior oblique projections for the triangle of Koch: implications from computed tomography.

BACKGROUND: Variability in the anatomy and orientation of the triangle of Koch (TK) complicates ablation procedures involving the atrioventricular (AV) node. We used CT angiography (CTA) to assess the anatomical TK orientation, the CS ostium direction, and the relationship between the two, and we validated an individualized CS-guided projection during ablation procedures. METHODS: In 104 patients without structural heart disease undergoing computed tomography (CT) angiography, TK orientations were determined in relation to the coronary sinus ostium (CSo) as well as two standard right anterior oblique (RAO) projection angles (30o and 45o) commonly used in ablation procedures. RESULTS: A CS-guided RAO projection (RAOCS) was shown to best track the orientation of the TK compared to RAO30° and 45°, with TK orientation strongly correlating with the CSo direction (r = 0.86, P < 0.001). In addition, the mean relative difference between the angle of the CSo and TK orientation was 5.54 ± 0.48°, consistent with a reduction in the degree of image shortening compared to traditional RAOs. Moreover, in vivo validation following ablation revealed that using a CS-guided projection limited the degree of on-screen image shortening compared to both the RAO30° and 45° in 25 patients with catheter ablation procedures. CONCLUSION: In hearts with a normal structure, the CSo direction offers a reliable predictor of the TK orientation which can be used to guide the projection of the TK during ablation procedures.

A new technique to salvage myocardium following the failure of thrombus aspiration in acute myocardial infarction: a case report.

BACKGROUND: The failure of aspiration thrombectomy may negatively impact outcomes in patients with acute myocardial infarction (AMI), but the available options are limited. CASE PRESENTATION: A 41-year-old man with chest pain for 2 h presented with ST-segment elevation myocardial infarction. Coronary angiography revealed a large filling defect extending from the distal left main (LM) coronary artery into the proximal left circumflex (LCX) coronary artery. The whole thrombus moved and occluded the proximal left anterior descending (LAD) artery, while the guidewire crossed the lesion. Dedicated manual aspiration thrombectomy (MAT) and balloon dilation failed to reduce thrombus burden. We considered thrombus extraction as impossible when it moved forward to occlude the middle LAD. To reduce infarct size, a new balloon-pushing technique was successfully performed to move the thrombus to the terminal LAD based on the actual condition of the LAD. The final angiogram demonstrated no stenosis in the LM artery and stent deployment was not performed. A 1-week follow-up coronary angiography revealed the complete resolution of thrombus and flow restoration in the left coronary artery. Intravascular ultrasound (IVUS) showed nonsignificant residual stenosis of the LM artery. No adverse events occurred during a 12-month follow-up period. CONCLUSION: This case suggests that the new balloon-pushing technique is a useful remedy if repeated MAT fails during AMI.

Altering 5-hydroxymethylcytosine modification impacts ischemic brain injury.

Epigenetic modifications such as cytosine methylation and histone modification are linked to the pathology of ischemic brain injury. Recent research has implicated 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine (5mC) via oxidation by ten-eleven translocation (Tet) enzymes, in DNA methylation-related plasticity. Here we show that 5hmC abundance was increased after ischemic injury, and Tet2 was responsible for this increase; furthermore, inhibiting Tet2 expression abolished the increase of 5hmC caused by ischemic injury. The decrease in 5hmC modifications from inhibiting Tet2 activity was accompanied by increased infarct volume after ischemic injury. Genome-wide profiling of 5hmC revealed differentially hydroxymethylated regions (DhMRs) associated with ischemic injury, and DhMRs were enriched among the genes involved in cell junction, neuronal morphogenesis and neurodevelopment. In particular, we found that 5hmC modifications at the promoter region of brain-derived neurotrophic factor (BDNF) increased, which was accompanied by increased BDNF mRNA, whereas the inhibition of Tet2 reduced BDNF mRNA and protein expression. Finally, we show that the abundance of 5hmC in blood samples from patients with acute ischemic stroke was also significantly increased. Together, these data suggest that 5hmC modification could serve as both a potential biomarker and a therapeutic target for the treatment of ischemic stroke.

Left ventricular mural thrombus and dual coronary embolization associated with hyperthyroid cardiomyopathy and atrial fibrillation: a case report.

BACKGROUND: The majority of acute myocardial infarction (AMI) events are caused by thrombotic occlusion of the coronary artery, secondary to atherosclerotic plaque erosion or rupture. However, coronary embolism (CE), while rare, is being increasingly recognized as an important cause of AMI. We present the case of a patient with multi-site coronary artery embolization associated with hyperthyroid-related cardiomyopathy and atrial fibrillation. CASE PRESENTATION: A 49-year-old female with a history of hyperthyroidism and atrial fibrillation (AF) was admitted to our hospital presenting with right upper limb pain and swelling. Initial transthoracic echocardiography demonstrated left ventricular apical mural thrombi and hyperthyroidism-induced cardiomyopathy. On the eighth day after admission, the patient developed sudden onset of severe chest pain and evidence of acute myocardial infarction (AMI). Emergency coronary angiography revealed multi-site coronary embolization of the left anterior descending artery and a large diagonal branch. Despite emergency thrombo-aspiration and balloon angioplasty, the patient went into ventricular fibrillation, from which she did not recover. CONCLUSION: Although rare, a fatal case of left ventricular thrombus and dual-vessel coronary embolism associated with hyperthyroid cardiomyopathy and atrial fibrillation is reported.

Unique Ventricular Tachycardia Originating from the Right Bundle Branch.

Ventricular tachycardia (VT), a common arrhythmia, frequently originates from in the right ventricular outflow tract, left ventricular outflow tract, aortic sinus, and left ventricular papillary muscle but infrequently from the His-Purkinje system, whereas the VT stemming from the right bundle branch has rarely been reported. Here we reported a case with of VT originating from the right bundle branch which was subsequently successfully treated with radiofrequency ablation and demonstrated the electrocardiac features of VT using an electrophysiological examination.

Local Geometric Effects on Stability and Energy Gap of Thiolate-Protected Gold Nanoparticles.

Thiolate-protected gold nanoclusters, Aum (SR)n , have potential applications in many fields due to their high stability and remarkable electronic properties. However, the controlling factors in determining the stability and HOMO-LUMO gap of Aum (SR)n remain controversial, despite decades of work on the topic. Through DFT calculations, including nonlocal many-body dispersion (MBD) interactions, the geometric and electronic properties of Aum (SR)n clusters are investigated. Calculations demonstrate that the MBD interactions are essential for correctly describing the geometry and energy of the clusters. Greater anisotropic polarization and more atoms distributed in the shell of the clusters lead to more pronounced MBD interactions and higher stability of the clusters. Furthermore, the HOMO-LUMO gap of the clusters strongly depends on the gold core. These results provide critical clues for understanding and designing Aum (SR)n clusters.

Amorphous Ni-B alloy nanoparticle film on Ni foam: rapid alternately dipping deposition for efficient overall water splitting.

It is highly attractive, but still remains challenging, to develop noble metal-free bifunctional electrocatalysts efficient for both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline media. In this letter, we describe the rapid electroless deposition of amorphous Ni-B nanoparticle film on Ni foam (Ni-B/Ni foam) by alternative dipping of Ni foam into Ni precursor and reducing solutions. This Ni-B/Ni foam acts as an efficient and durable 3D catalytic electrode for water splitting, affording 100 mA cm(-2) at 360 mV overpotential for the OER and 20 mA cm(-2) at 125 mV overpotential for the HER in 1.0 M KOH, and its two-electrode electrolyzer demands a cell voltage of 1.69 V to afford 15 mA cm(-2) water-splitting current. Moreover, the catalyst loading can be easily tuned and this alternately dipping deposition technique works universally for other conductive substrates.

Highly efficient electrochemical hydrogen evolution based on nickel diselenide nanowall film.

In this letter, we report on hydrothermal growth of nickel diselenide nanowall film on carbon cloth (NiSe2 NW/CC) through topotactic transformation from a Ni(OH)2 precursor based on anion exchange reactions. When tested as an integrated 3D hydrogen-evolving cathode in strongly acidic media, NiSe2 NW/CC exhibits outstanding catalytic activity superior to its powder counterpart and strong long-term durability. It displays 10 and 100 mA cm(-2) at overpotentials of 145 and 183 mV, respectively, with its catalytic activity being retained for 40 h.

Clinical value of a self-designed training model for pinpointing and puncturing trigeminal ganglion.

OBJECTIVES. A training model was designed for learners and young physicians to polish their skills in clinical practices of pinpointing and puncturing trigeminal ganglion. METHODS. A head model, on both cheeks of which the deep soft tissue was replaced by stuffed organosilicone and sponge while the superficial soft tissue, skin and the trigeminal ganglion were made of organic silicon rubber for an appearance of real human being, was made from a dried skull specimen and epoxy resin. Two physicians who had experiences in puncturing foramen ovale and trigeminal ganglion were selected to test the model, mainly for its appearance, X-ray permeability, handling of the puncture, and closure of the puncture sites. Four inexperienced physicians were selected afterwards to be trained combining Hartel's anterior facial approach with the new method of real-time observation on foramen ovale studied by us. RESULTS. Both appearance and texture of the model were extremely close to those of a real human. The fact that the skin, superficial soft tissue, deep muscles of the cheeks, and the trigeminal ganglion made of organic silicon rubber all had great elasticity resulted in quick closure and sealing of the puncture sites. The head model made of epoxy resin had similar X-ray permeability to a human skull specimen under fluoroscopy. The soft tissue was made of radiolucent material so that the training can be conducted with X-ray guidance. After repeated training, all the four young physicians were able to smoothly and successfully accomplish the puncture. CONCLUSION. This self-made model can substitute for cadaver specimen in training learners and young physicians on foramen ovale and trigeminal ganglion puncture. It is very helpful for fast learning and mastering this interventional operation skill, and the puncture accuracy can be improved significantly with our new method of real-time observation on foramen ovale.

Scalable synthesis of Au@CeO2 nanozyme for development of colorimetric lateral flow immunochromatographic assay to sensitively detect heart-type fatty acid binding protein.

Nanozymes with core@shell nanostructure are considered promising biolabeling materials for their multifunctional properties. In this work, a simple one-pot strategy has been proposed for scalable synthesis of gold@cerium dioxide core@shell nanoparticles (Au@CeO2 NPs) with strong localized surface plasmon resonance (LSPR) absorption and high peroxidase-like catalytic activity by redox reactions of Ce3+ ions and AuCl4- ions in diluted ammonia solution under room temperature. A colorimetric lateral flow immunochromatographic assay (LFIA) has been successfully fabricated for sensitive detection of heart-type fatty acid binding protein (H-FABP, an early cardiac biomarker) by using the Au@CeO2 NPs as reporters. The as-developed LFIA with Au@CeO2 NP reporter (termed as Au@CeO2-LFIA) exhibits a dynamic range of nearly two orders of magnitude, and a limit of detection (LOD) as low as 0.35 ng mL-1 H-FABP with nanozyme-triggered 3,3',5,5'-tetramethylbenzidine (TMB) colorimetric amplification. Furthermore, the practicality of Au@CeO2-LFIA has been demonstrated by profiling the concentrations of H-FABP in 156 blood samples of acute myocardial infarction (AMI) patients, and satisfactory results are obtained.

LSD1 modulates the bone metastasis of breast cancer cells through hnRNPA2B1-mediated sorting of exosomal miRNAs.

Bone metastasis is a key contributor to morbidity and mortality of breast cancer patients. We have previously shown that exosomal miRNAs derived from LSD1 knockdown (KD) breast cancer cells inhibit osteoblast differentiation and promote osteoclast differentiation. However, how LSD1 regulates exosomal miRNAs and whether miRNAs promote bone metastasis through the formation of pre-metastatic niches remains unclear. In vivo experiments demonstrates that exosomes derived from LSD1 KD breast cancer cells significantly promoted bone metastasis. To explore the mechanism underlying the effect of LSD1 on exosomes in breast cancer cells, exosomal and cellular miRNAs from control, LSD1 KD, and rescue cells were sequenced. Interestingly, approximately 80% of LSD1-associated miRNAs were downregulated in exosomes from LSD1 KD cells. The consensus sequence UAGGGC, was identified in many miRNAs downregulated in LSD1 KD exosomes. We found that hnRNPA2B1 regulated the exosomal sorting of miR-6881-3p and some other miRNAs. LSD1 deficiency reduced hnRNPA2B1 expression in breast cancer cells by decreasing the level of H3K9me2 demethylation in the promoter region of the hnRNPA2B1 gene. Our study revealed that LSD1 plays a crucial role in the regulation of exosomal sorting of miRNA.

A feasibility study on pinpointing the branches of trigeminal nerve in radiofrequency ablation.

OBJECTIVE: To propose a pinpointing method and to obtain technique parameters for puncture of the branches of the trigeminal nerve through anatomical radiological study. DESIGN: Trigeminal ganglions and intracranial branches of 25 pieces (50 sides) of adult skull wet-specimens were dissected and coated with contrast agent. X-ray images of the skull in lateral cranial position were collected with the tube inclining towards head at 15°, 20° and 25°. 'Porus-Clinoid Line' and 'FO-PC axis' were delineated on the images. The latter set as the base line, Point A, B and C were settled separately as the upper rim of the trigeminal ganglion, the axis of Brach V2 and the junction of the extended border lines of Branch V2 and V3 all intersected with it. The collected data was processed afterwards. RESULTS: In the cases of 50 sides, the maximum value of the 'FO-PC Distance' was 17.8 mm; Distance A, 6.6 mm; Distance B, 10.1 mm; and Distance C, 6.6 mm, while the minimum of each was 9.4 mm, 0.3 mm, 4.4 mm and 6.6 mm respectively. Ratios of the 'FO-PC Distance' to Distance B were respectively 2.00 ± 0.15 mm, 1.98 ± 0.15 mm and 1.95 ± 0.16 mm when tube inclined towards head at angles of 15°, 20° and 25°; to Distance C were 3.06 ± 0.53 mm, 3.36 ± 0.60 mm and 3.75 ± 0.96 mm and to Distance A were 10.65 ± 9.17 mm, 7.33 ± 5.28 mm, 5.16 ± 2.30 mm under the same condition. CONCLUSION: The results showed that Distances from each branch of trigeminal nerve to the medial rim of foramen ovale vary on different individuals while the proportional relationship between each branch and 'FO-PC Distance' has regularity.

Targeting mitochondrial dynamics proteins for the treatment of doxorubicin-induced cardiotoxicity.

Doxorubicin (DOX) is an extensively used chemotherapeutic agent that can cause severe and frequent cardiotoxicity, which limits its clinical application. Although there have been extensive researches on the cardiotoxicity caused by DOX, there is still a lack of effective treatment. It is necessary to understand the molecular mechanism of DOX-induced cardiotoxicity and search for new therapeutic targets which do not sacrifice their anticancer effects. Mitochondria are considered to be the main target of cardiotoxicity caused by DOX. The imbalance of mitochondrial dynamics characterized by increased mitochondrial fission and inhibited mitochondrial fusion is often reported in DOX-induced cardiotoxicity, which can result in excessive ROS production, energy metabolism disorders, cell apoptosis, and various other problems. Also, mitochondrial dynamics disorder is related to tumorigenesis. Surprisingly, recent studies show that targeting mitochondrial dynamics proteins such as DRP1 and MFN2 can not only defend against DOX-induced cardiotoxicity but also enhance or not impair the anticancer effect. Herein, we summarize mitochondrial dynamics disorder in DOX-induced cardiac injury. Furthermore, we provide an overview of current pharmacological and non-pharmacological interventions targeting proteins involved in mitochondrial dynamics to alleviate cardiac damage caused by DOX.