miR-200b-3p accelerates progression of pituitary adenomas by negatively regulating expression of RECK.

MicroRNA (miR)-200b-3p has been associated with many tumors, but its involvement in pituitary adenoma is unclear. This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment. Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA. As well, the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay. The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization. Transfection of the miR-200b-3p inhibitor and small interfering-RECK (si-RECK) was verified by qPCR. GH3 cell viability and proliferation were detected using CCK8 and EdU assays. Apoptosis was detected by flow cytometry and western blotting. Wound healing and Transwell assays were used to detect cell migration and invasion. The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments. miR-200b-3p was highly expressed in pituitary tumor tissue. Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis, inhibited invasion and migration, and inhibited the expression of matrix metalloproteinases. Interestingly, miR-200b-3p negatively regulated RECK. The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues. Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors, and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression. In summary, this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK. The findings provide a new target for the treatment of pituitary adenoma.

CAR T treatment beyond cancer: Hope for immunomodulatory therapy of non-cancerous diseases.

Engineering a patient's own T cells to accurately identify and eliminate cancer cells has effectively cured individuals afflicted with previously incurable hematologic cancers. These findings have stimulated research into employing chimeric antigen receptor (CAR) T therapy across various areas within the field of oncology. However, evidence from both clinical and preclinical investigations emphasize the broader potential of CAR T therapy, extending beyond oncology to address autoimmune disorders, persistent infections, cardiac fibrosis, age-related ailments and other conditions. Concurrently, the advent of novel technologies and platforms presents additional avenues for utilizing CAR T therapy in non-cancerous contexts. This review provides an overview of the rationale behind CAR T therapy, delineates ongoing challenges in its application to cancer treatment, summarizes recent findings in non-cancerous diseases, and engages in discourse regarding emerging technologies that bear relevance. The review delves into prospective applications of this therapeutic approach across a diverse range of scenarios. Lastly, the review underscores concerns related to precision and safety, while also outlining the envisioned trajectory for extending CAR T therapy beyond cancer treatment.

Deciphering the link: ferroptosis and its role in glioma.

Glioma, as the most frequently occurring primary malignancy in the central nervous system, significantly impacts patients' quality of life and cognitive abilities. Ferroptosis, a newly discovered form of cell death, is characterized by significant iron accumulation and lipid peroxidation. This process is fundamentally dependent on iron. Various factors inducing ferroptosis can either directly or indirectly influence glutathione peroxidase, leading to reduced antioxidant capabilities and an increase in lipid reactive oxygen species (ROS) within cells, culminating in oxidative cell death. Recent research indicates a strong connection between ferroptosis and a range of pathophysiological conditions, including tumors, neurological disorders, ischemia-reperfusion injuries, kidney damage, and hematological diseases. The regulation of ferroptosis to intervene in the progression of these diseases has emerged as a major area of interest in etiological research and therapy. However, the exact functional alterations and molecular mechanisms underlying ferroptosis remain to be extensively studied. The review firstly explores the intricate relationship between ferroptosis and glioma, highlighting how ferroptosis contributes to glioma pathogenesis and how glioma cells may resist this form of cell death. Then, we discuss recent studies that have identified potential ferroptosis inducers and inhibitors, which could serve as novel therapeutic strategies for glioma. We also examine the current challenges in targeting ferroptosis in glioma treatment, including the complexity of its regulation and the need for precise delivery methods. This review aims to provide a comprehensive overview of the current state of research on ferroptosis in glioma, offering insights into future therapeutic strategies and the broader implications of this novel cell death pathway in cancer biology.

Detection of trace chlorine pollutants in recycled pulp using gas chromatography-tandem mass spectrometry with response surface-optimized carbon structure online catalysis.

RATIONALE: Chlorinated aromatics and alkanes are widely used for their flame retardancy, but they need to be monitored when used in recycled pulp. This paper reports the use of palladium acetate/activated carbon (Pa/Ac) activated by nitric acid as an online catalyst to determine chlorinated aromatics and chlorinated alkanes in recycled paper products using gas chromatography-tandem mass spectrometry (GC-MS/MS), which significantly improves the sensitivity of the method and remarkably lowers the detection limits. METHODS: The Pa/Ac catalyst was prepared using a self-made catalytic device and used as key to the online catalytic conversion of target chlorinated aromatic hydrocarbons and chlorinated alkanes for GC-MS/MS analysis. The response surface model was used to optimize catalytic conditions. Then GC-MS/MS in the multireaction monitoring mode with online catalysis was applied for the analysis of polychlorinated biphenyls, polychlorinated terphenyls, polychlorinated naphthalene, and chlorinated paraffins (CP) in recycled paper products. RESULTS: Compared with traditional methods, the Pa/Ac catalyst can transform chlorinated aromatic hydrocarbons into aromatic hydrocarbons through dechlorination hydrogenation, thus lowering the detection limit of the GC-MS/MS method significantly. It can transform paraffin chloride into the corresponding alkane to better distinguish short-chain, medium-chain, or long-chain CPs. Online catalytic conversion significantly improved the sensitivity and reproducibility (88.7%-113.1%) of the method. Tissue samples with various concentration levels of chlorinated aromatics and chlorinated alkanes were tested. The linearity range of the reduced target compounds in the reduction product solution was 0.02-1.00 µg/ml (R2  > 0.995). The quantitative detection limit was 0.03-0.05 µg/kg, and relative standard deviation was less than 6.9%. CONCLUSION: This study was the first to introduce the Pa/Ac catalytic device as an online catalytic unit in the determination of chlorinated aromatics and chlorinated alkanes using the GC-MS/MS method. The target compounds were converted into alkanes and aromatic hydrocarbons with unchanged carbon structures, and the method could achieve a low detection limit with no need for high-end methods such as GC-chemical ionization ion source (CI)-MS or high-resolution mass spectrometry. These methods are suitable for the determination of chlorine pollutants in recycled paper and its raw materials.

Early Assessment of Cardiac Function by Echocardiography in Patients with Gestational Diabetes Mellitus.

Objective: To offer a baseline for clinical diagnosis, echocardiography was performed to evaluate the disparities in heart function comparing pregnant women with diabetes mellitus (GDM) and ordinary pregnant women. Methods: A prospective case-control study is being conducted on pregnant women with or without gestational diabetes. The sample size for both the intervention and control groups is the same: no diabetes diagnosis or previous forms, a single pregnancy, and no issues (such as preeclampsia or fetal growth restriction). The females were all subjected to routine echocardiograms to examine the morphology and function of their left and right hearts. Results: In the research, 51 women with GDM and 50 healthy controls volunteered. Women with GDM had a significantly higher heartrate (82 ± 9 vs. 74 ± 8), left ventricular (LV) relative wall thickness (0.39 ± 0.06 vs. 0.31 ± 0.07; P < 0.001), LV early diastolic transmitral valve velocity (E) (0.79 ± 0.14 vs. 0.72 ± 0.13 m/s; P = 0.031), and LV late diastolic implementing regulations valve velocity (0.6). Speckle-tracking analysis showed significant decrease in LV right ventricular (RV). A study indicated a reduced pulmonary acceleration time (59 ± 9 vs. 68 ± 12 ms; P = 0.001), RV E/A ratio (1.21 ± 0.19 vs. 1.31 ± 0.31; P = 0.022), and a greater RV myocardial systolic annular velocity (0.17 ± 0.03 vs. 0.12 ± 0.03; P = 0.023). Conclusions: Our results revealed that the heart function of diabetic pregnant women differed considerably from that of the control group, such as LV-RWT, LV diastolic transmitral valve speed, and LV late diastolic transmitral valve speed. Given these results, further research into the postpartum cardiovascular healing of pregnant women with gestational diabetes mellitus is required.

The Application Value of Three-Dimensional Power Doppler Ultrasound in Fetal Growth Restriction.

In this study, the application value of three-dimensional power Doppler ultrasound (3D-PDU) in fetal growth restriction (FGR) is explored. The retrospective cohort study enrolled pregnant women (with a gestational week of 11-13 + 6 weeks) who received routine health care in the obstetrics and gynecology clinic of our hospital from January 2020 to January 2021. The placentae were scanned using 3D-PDU, and the subjects were followed up until delivery. The fetuses were divided into the control group (n = 322) and FGR group (n = 44) according to their birth weight. There was no significant difference in nuchal translucency (NT), crown-rump length (CRL), and placental volume (PV) during the first trimester between the two groups (P > 0.05). Compared with the control group, the FGR group showed significantly lower levels of vascularisation index (VI), flow index (FI), and vascularisation flow index (VFI) and a higher incidence of fetal distress and neonatal asphyxia (P < 0.05). The FGR group showed a longer gestational week at birth, a higher probability of cesarean section, and a lower 5-minute Apgar score than the control group (P < 0.05). The VI, FI, and VFI of the control group were significantly higher than those of the FGR group. Pearson analysis showed that birth weight was positively correlated with VI and FI (P < 0.05). 3D-PDU assesses the blood perfusion of the fetus and placenta in the first trimester and predicts the pregnancy outcome, which shows great potential in the early diagnosis of FGR.

Traditional Chinese Medicine Text Similarity Calculation Model Based on the Bidirectional Temporal Siamese Network.

The text similarity calculation plays a crucial role as the core work of artificial intelligence commercial applications such as traditional Chinese medicine (TCM) auxiliary diagnosis, intelligent question and answer, and prescription recommendation. However, TCM texts have problems such as short sentence expression, inaccurate word segmentation, strong semantic relevance, high feature dimension, and sparseness. This study comprehensively considers the temporal information of sentence context and proposes a TCM text similarity calculation model based on the bidirectional temporal Siamese network (BTSN). We used the enhanced representation through knowledge integration (ERNIE) pretrained language model to train character vectors instead of word vectors and solved the problem of inaccurate word segmentation in TCM. In the Siamese network, the traditional fully connected neural network was replaced by a deep bidirectional long short-term memory (BLSTM) to capture the contextual semantics of the current word information. The improved similarity BLSTM was used to map the sentence that is to be tested into two sets of low-dimensional numerical vectors. Then, we performed similarity calculation training. Experiments on the two datasets of financial and TCM show that the performance of the BTSN model in this study was better than that of other similarity calculation models. When the number of layers of the BLSTM reached 6 layers, the accuracy of the model was the highest. This verifies that the text similarity calculation model proposed in this study has high engineering value.

Effectiveness and safety of different traditional Chinese medicines for Coronavirus disease 2019: A protocol for systematic review and network meta-analysis.

INTRODUCTION: The effectiveness of different Traditional Chinese Medicine in the treatment of COVID-19 is worthy of attention, but the efficacy and safety of different Traditional Chinese Medicine in the treatment of COVID-19 have not yet been compared, based on network meta-analysis. METHODS AND ANALYSIS: The 2 members independently searched 7 databases according to the retrieval strategy, and the retrieval time was from the beginning of the establishment of the database to June 19, 2021. Then the title was imported into the EndNote Software AQ8 (V.X9), and the duplicate literature was deleted successively, the nonconforming articles were deleted in the title reading, and finally the full text was read to determine the articles included in the study. The Cochrane Collaboration's Tool will be used to evaluate the article quality, and Stata Statistical Software (Version 14.0, Stata Corporation, College Station, TX) will be used for data analysis. Levels of evidence are evaluated according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument. RESULTS: The efficacy and safety of different Traditional Chinese Medicine in the treatment of COVID-19 were evaluated, and the order was determined according to the value of sucre. CONCLUSION: This study will provide evidence for the treatment of COVID-19 with TCM therapy, and provide ideas for the clinical treatment of COVID-19. INPLASY REGISTRATION NUMBER: No. INPLASY202160092.

The diagnosis of a giant cardiac malignant lymphoma in the right ventricle: a case report.

Cardiac lymphoma is extremely rare in patients with normal immune function and difficult to identify through routine examinations in patients with atypical clinical manifestations, making early diagnosis very difficult. We reported a 71-year-old male patient who was repeatedly diagnosed of pulmonary infection, suspected lung tumour, and Kimura disease in other hospital due to cough, expectoration, and dyspnoea. Later on, the patient visited our hospital due to heart failure and epistaxis. Transthoracic echocardiogram confirmed the presence of a space-occupying lesion in the right heart, cardiac magnetic resonance imaging preliminarily determined the nature of this lesion, finally, 18 F-fluorodeoxyglucose positron-emission tomography/computed tomography, and nasal mass biopsy confirmed the diagnosis of cardiac malignant lymphoma, and the pathological type was diffuse large B-cell lymphoma.

Formononetin may protect aged hearts from ischemia/reperfusion damage by enhancing autophagic degradation.

Myocardial infarction is a leading cause of mortality worldwide, and timely blood/oxygen reperfusion may substantially improve the outcome of infarction. However, ischemia/reperfusion (I/R) may cause severe side effects through excess reactive oxygen species generation. To develop novel methods to relieve I/R induced cell damage, the present study used a component of traditional Chinese medicine. In the present study, isolated heart tissue from aged mice and H9C2 cells with chemically­induced aging were used as experimental subjects, and it was demonstrated that formononetin was able to alleviate I/R­induced cell or tissue apoptosis. By applying formononetin to I/R­damaged tissue or cells, it was demonstrated that formononetin was able to enhance autophagy and thus alleviate I/R­induced cell damage. Furthermore, it was observed that I/R was able to inhibit lysosomal degradation processes in aged tissues or cells by impairing the lysosome acidification level, and formononetin was able to reverse this process via the re­acidification of lysosomes. In conclusion, the present study demonstrated that formononetin was able to alleviate I/R­induced cellular apoptosis in aged cells by facilitating autophagy.

Heterogeneity of insulin resistance and beta cell dysfunction in gestational diabetes mellitus: a prospective cohort study of perinatal outcomes.

BACKGROUND: Insulin resistance and beta cell dysfunction were reported to be responsible for gestational diabetes mellitus (GDM). However, little is known about the heterogeneity of these factors and its influences on perinatal outcomes. We investigated whether subtypes of insulin resistance and beta cell dysfunction in gestational diabetes mellitus have different impacts on perinatal outcomes. METHODS: In this prospective cohort study, we followed 554 pregnant women and glucose challenge test was performed at 24-28th weeks of their gestation. Women with plasma glucose ≥ 7.8 mmol/L would be included and advised to undergo the diagnostic 75-g, 3-h oral glucose tolerance test. According to indices of measuring insulin resistance or beta cell function were below the 25th percentile of women with normal glucose tolerance (NGT), women with GDM were defined as three subtypes: GDM with the beta cell dysfunction, GDM with the insulin resistance defect or GDM with both traits mentioned above (GDM-mixed). Perinatal outcomes were documented. RESULTS: The levels of prepregnancy and maternal BMI in the GDM-mix group were higher compared to women in the NGT group (23.2 ± 4.0 vs 20.8 ± 3.7 kg/m2, P < 0.001; 24.5 ± 4.3 vs 21.8 ± 3.4 kg/m2, P < 0.001, respectively). Furthermore, women in GDM-mix group more likely to be subjected to LGA (P = 0.008) adverse perinatal outcomes (P = 0.005), although these differences were normalized after adjusting age, prepregnancy and maternal BMI (GDM-mix vs. NGT: P = 0.141 for LGA and P = 0.186 for adverse outcomes). On the other hand, all perinatal outcomes were similar between other two GDM subgroups and NGT group. CONCLUSIONS: Women with GDM display respective characteristics on metabolism disorders and confer discriminating risks of adverse perinatal outcomes because of this heterogeneity.

Early elevated alkaline phosphatase increases the risk of large-for-gestational-age birth weight in pregnant women with normal glucose tolerance.

AIMS: The aim of this study was to assess the association between levels of alkaline phosphatase (ALP) in early pregnancy and the incidence of large-for-gestational-age (LGA) neonates in pregnant women without gestational diabetes mellitus. METHODS: A prospective cohort was carried out in 544 women and their biochemical parameters including serum ALP and demographic characteristics were collected in 13-16th gestational week. At 24-28th weeks of gestation, 50 g oral glucose challenge test and oral 75 g glucose tolerance test was performed. LGA was defined as birth weight ≥ 90th percentile for completed week of gestational age based on the sex-specific growth curves. Logistic regression and receiver operating characteristic analysis were utilized to identify independent risk factors and odds ratio among ALP quartiles for incidence of LGA. RESULTS: Women diagnosed as LGA held higher level of ALP than women in non-LGA group (P = 0.008). Moreover, ALP (odds ratio (OR) 1.05 [95% confidence interval (CI): 1.00, 1.10]) was the independent risk factors associated with LGA. Compared with ALP quartile 1, women in quartile 4 had more than 2.5-fold increased odds of LGA (OR 3.78, 95% CI: 1.10, 13.02), and the risk reached 4 times after adjusting several covariates (OR 4.15, 95% CI: 1.14,15.13). CONCLUSIONS: A significantly increased risk of LGA was associated with higher serum concentrations of ALP in pregnant women with NGT, even it is in normal reference range.

Differentially methylated circulating DNA: A novel biomarker to monitor beta cell death.

Diabetes mellitus (DM) is a metabolic disorder of glucose homeostasis caused by insufficient secretion or inadequate action of insulin. Nowadays, the increased morbidity of DM is a worldwide issue. Pancreatic beta cell death plays a key role in the progress of DM, especially Type 1 diabetes (T1D). Traditional biomarkers, such as C-peptide and islet autoimmune antibodies are limited to reflect beta cell death and to identify high risk patients in the clinical practice. Recently, a novel biomarker, differentially methylated circulating DNA, has become a research hotspot. It has better sensitivity and specificity in the detection of beta cell death. Assays of beta cell-derived differentially methylated insulin DNA in serum are helpful to predict the possibility to develop T1D in the high risk population. They have also been applied to evaluate beta cell death in Type 2 diabetes (T2D), gestational diabetes mellitus (GDM), islet transplantation and islet specific immune therapy. Although more studies are needed to identify the best methylation target sites in the INS gene, differentially methylated circulating DNA may be a good method to evaluate the progression and prognosis of islet related diseases in the future.

Effects of losartan on vasomotor function and canonical transient receptor potential channels in the aortas of sinoaortic denervation rats.

Increased short-term blood pressure variability (BPV) is strongly correlated with target organ damage. However, the molecular mechanisms underlying abnormal BPV-induced organ damage and effective therapeutic targets are poorly understood. The purpose of this study was to investigate the effects of losartan on vasomotor function and canonical transient receptor potential (TRPC) channels in the aortas of rats with arterial pressure lability induced by sinoaortic denervation (SAD). SAD was performed in male Sprague-Dawley rats at the age of 10 weeks. The experiment included sham-operated (Sham), SAD, and losartan-treated SAD (SAD+Los) groups. After 8 weeks of treatment, hemodynamic parameters were measured via catheterization, thoracic aortic vasomotor functions were evaluated using a physiological vascular ring tension recording system, and TRPC1 and 6 mRNA and protein expression levels in the endothelial cells (ECs) and smooth muscle cells (SMCs) of the thoracic aorta were determined via reverse transcription polymerase chain reaction (RT-PCR) and Western-blotting, respectively. Compared with Sham rats, SAD rats exhibited significantly increased BPV, enhanced norepinephrine-induced aortic contraction, and attenuated acetylcholine-induced aortic relaxation. Both the mRNA and the protein expression levels of TRPC1 and 6 were significantly downregulated in the ECs and upregulated in the SMCs of the thoracic aortas of SAD rats. Losartan treatment prevented these SAD-induced changes. In conclusion, losartan efficiently prevented vasomotor function impairment in SAD rats by reducing BPV and regulating TRPC1 and 6 expression levels.

Comparative study on the effects of apple peel polyphenols and apple flesh polyphenols on cardiovascular risk factors in mice.

Apple consumption has been demonstrated to be associated with reduced risk of cardiovascular disease, and the beneficial effect is probably due to the polyphenols in apple. Here, we for the first time evaluated and compared the in vivo effects of the polyphenolic extracts of apple peels (PAP) and apple fleshes (PAF) on blood pressure, vascular endothelial function, lipid metabolism and insulin resistance. A high-fat and high-fructose (HFHF) diet was used to cause cardiovascular disorders in mice, with blood pressure, serum ET-1, TC, TG, LDL-C, glucose and insulin levels increased, and serum NO and HDL-C levels decreased. Mice administered with 250 mg/kg of PAP and PAF for 28 days showed lower blood pressure, improved endothelial function, ameliorated lipid homeostasis and decreased insulin resistance compared with HFHF-fed mice. Furthermore, PAP exhibited much more potent cardioprotective effects than PAF in mice. Quantification and phenolic profile analysis showed that PAP contained remarkably higher amount of total phenolics and total flavonoids than PAF, and this may be the reason for the relatively stronger efficacy of PAP. This study demonstrates that apple polyphenols possess potential cardioprotective effects, and suggests that apple, especially apple peel, may be excellent source for exploration of preventive agents against cardiovascular disorders.

Correlation between ambulatory blood pressure variability and vasodilator function in middle-aged normotensive individuals.

OBJECTIVE: The aim of this study was to investigate the association between ambulatory blood pressure variability and vasodilator function in a cohort of normotensive middle-aged individuals. PARTICIPANTS AND METHODS: This was a cross-sectional study of 285 randomly selected 40-59-year-old normotensive participants who underwent 24-h ambulatory blood pressure monitoring and brachial artery ultrasound assessment. Systolic and diastolic blood pressure variability (BPV) of 24-h, daytime, and night-time were calculated using the coefficients of variation (CV) and the average real variability (ARV) index. Brachial arterial endothelium-dependent vasodilation (EDD) was assessed in response to increased flow and endothelium-independent vasodilation (EID) was assessed in response to nitroglycerin. Relationships were explored using univariate and multivariate linear regression. RESULTS: The EDD were negatively associated with the CV of 24-h systolic blood pressure (SBP), the ARV of 24-h SBP, and diastolic blood pressure (DBP) in univariate analysis. However, the CV and ARV of 24-h SBP remained associated independently with % EDD in multivariate analysis. In addition, the mean levels of 24-h SBP and DBP, the CV of 24-h SBP and DBP, the ARV of 24-h SBP and DBP, the CV of daytime SBP, and the ARV of daytime DBP were all associated with % EID. However, in a multiple linear regression model, adjusting for covariates, only the CV and ARV of 24-h SBP, and the ARV of 24-h DBP were correlated negatively but weakly with % EID. CONCLUSION: Our results indicated that a higher 24-h BPV was associated independently with decreased endothelial-dependent and endothelial-independent vasodilator functions in a middle-aged normotensive population. Although 24-h BPV was associated with vasodilator function, relationships were attenuated after adjusting for covariates.

Evaluation of Right Ventricular Systolic Function in Patients With Chronic Pulmonary Heart Disease by 2-Dimensional Speckle-Tracking Echocardiography.

OBJECTIVES: To investigate the value of 2-dimensional (2D) speckle-tracking echocardiography for assessing right ventricular (RV) systolic function in patients with chronic pulmonary heart disease (CPHD) and the correlation of its parameters with the right ventricular ejection fraction (RVEF) on cardiac magnetic resonance imaging (MRI). METHODS: According to pulmonary arterial systolic pressure, 80 patients with CPHD and tricuspid regurgitation were divided into 2 groups: 42 with mild pulmonary hypertension (PH; 30-50 mm Hg) and 38 with moderate or severe PH (≥50 mm Hg); 41 control participants were recruited. All participants underwent 2D speckle-tracking echocardiography and cardiac MRI. The longitudinal peak systolic strain and longitudinal peak systolic strain rate were measured by echocardiography in each segment of the RV free wall and interventricular septum and compared with the RVEF on cardiac MRI. RESULTS: Strain values in all segments of the RV free wall and interventricular septum were lower in the mild PH group than the control group (P < .05). Strain rate values in the apical segment of the RV free wall and basal segment of the interventricular septum were lower in the mild PH group than the control group (P< .05). Strain and strain rate values in all segments of the RV free wall and interventricular septum were lower in the moderate or severe PH group than the control group (P < .05). Strain and strain rate values in all segments of the RV free wall and interventricular septum were lower in the moderate or severe PH group than the mild PH group (P< .05). Strain and strain rate values in all segments of the RV free wall and the interventricular septum correlated with the RVEF (P < .001). CONCLUSIONS: The ability of speckle-tracking echocardiography to directly monitor RV myocardial function may allow early sensitive detection of subclinical myocardial dysfunction in patients with CPHD, with better risk stratification and timely institution of therapy.

The Value of 3D Printing Models of Left Atrial Appendage Using Real-Time 3D Transesophageal Echocardiographic Data in Left Atrial Appendage Occlusion: Applications toward an Era of Truly Personalized Medicine.

AIMS AND OBJECTIVES: The objective of this study was to assess the clinical feasibility of generating 3D printing models of left atrial appendage (LAA) using real-time 3D transesophageal echocardiogram (TEE) data for preoperative reference of LAA occlusion. BACKGROUND: Percutaneous LAA occlusion can effectively prevent patients with atrial fibrillation from stroke. However, the anatomical structure of LAA is so complicated that adequate information of its structure is essential for successful LAA occlusion. Emerging 3D printing technology has the demonstrated potential to structure more accurately than conventional imaging modalities by creating tangible patient-specific models. Typically, 3D printing data sets are acquired from CT and MRI, which may involve intravenous contrast, sedation, and ionizing radiation. It has been reported that 3D models of LAA were successfully created by the data acquired from CT. However, 3D printing of the LAA using real-time 3D TEE data has not yet been explored. METHODS: Acquisition of 3D transesophageal echocardiographic data from 8 patients with atrial fibrillation was performed using the Philips EPIQ7 ultrasound system. Raw echocardiographic image data were opened in Philips QLAB and converted to 'Cartesian DICOM' format and imported into Mimics® software to create 3D models of LAA, which were printed using a rubber-like material. The printed 3D models were then used for preoperative reference and procedural simulation in LAA occlusion. RESULTS: We successfully printed LAAs of 8 patients. Each LAA costs approximately CNY 800-1,000 and the total process takes 16-17 h. Seven of the 8 Watchman devices predicted by preprocedural 2D TEE images were of the same sizes as those placed in the real operation. Interestingly, 3D printing models were highly reflective of the shape and size of LAAs, and all device sizes predicted by the 3D printing model were fully consistent with those placed in the real operation. Also, the 3D printed model could predict operating difficulty and the presence of a peridevice leak. CONCLUSIONS: 3D printing of the LAA using real-time 3D transesophageal echocardiographic data has a perfect and rapid application in LAA occlusion to assist with physician planning and decision making.

Polydatin post-treatment alleviates myocardial ischaemia/reperfusion injury by promoting autophagic flux.

Polydatin (PD), a resveratrol (RES) glycoside, has a stronger antioxidative effect than RES. It is known that RES is an autophagic enhancer and exerts a cardioprotective effect against ischaemia/reperfusion (I/R) injury. However, the effect of PD post-treatment on myocardial I/R injury remains unclear. In the present study, we investigated the influences of PD post-treatment on myocardial I/R injury and autophagy. C57BL/6 mice underwent left coronary artery (LCA) occlusion and cultured neonatal rat cardiomyocytes (NRCs) subjected to hypoxia were treated with vehicle or PD during reperfusion or re-oxygenation. We noted that PD enhanced autophagy and decreased apoptosis during I/R or hypoxia/reoxygenation (H/R), and this effect was antagonized by co-treatment with adenovirus carrying short hairpin RNA for Beclin 1 and 3-methyladenine (3-MA), an autophagic inhibitor. Compared with vehicle-treated mice, PD-treated mice had a significantly smaller myocardial infarct size (IS) and a higher left ventricular fractional shortening (LVFS) and ejection fraction (EF), whereas these effects were partly reversed by 3-MA. Furthermore, in the PD-treated NRCs, tandem fluorescent mRFP-GFP-LC3 assay showed abundant clearance of autophagosomes with an enhanced autophagic flux, and co-treatment with Bafilomycin A1 (Baf), a lysosomal inhibitor, indicated that PD promoted the degradation of autolysosome. In addition, PD post-treatment reduced mitochondrial membrane potential and cellular reactive oxygen species (ROS) production in NRCs, and these effects were partially blocked by Baf. These findings indicate that PD post-treatment limits myocardial I/R injury by promoting autophagic flux to clear damaged mitochondria to reduce ROS and cell death.

Assessment of Ticagrelor Versus Clopidogrel Treatment in Patients With ST-elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

AIMS: Ticagrelor improves the clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). However, few studies have directly compared the efficacy and safety of ticagrelor against clopidogrel, an oral, thienopyridine-class antiplatelet drug. This study compared the efficacy and safety of ticagrelor and clopidogrel in patients with STEMI undergoing PPCI. METHODS: We enrolled 400 patients with STEMI undergoing PPCI at the Zhujiang Hospital of Southern Medical University and the First Hospital of Qinhuangdao, China, between January 01, 2013 and April 30, 2015. All patients received 300 mg of aspirin and were randomized to receive one of the following treatments: (1) a loading dose of clopidogrel (600 mg) before PPCI followed by clopidogrel (75 mg once daily for 1 year) post PPCI or (2) a loading dose of ticagrelor (180 mg) before PPCI followed by ticagrelor (90 mg twice daily for 1 year) post PPCI. Some patients were treated by intracoronary bolus of a glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor [tirofiban (10 µg/kg) plus maintenance infusion (0.15 µg·kg·min) for 24-36 hours] in accordance with specified guidelines. The primary end points evaluated were major adverse cardiovascular and cerebrovascular event (MACCE) [defined as a composite of overall death, myocardial infarction (MI), unplanned revascularization, or stroke], stent thrombosis, and the composite end point of CV death, nonfatal MI, and stroke. The supplemental use of GPIIb/IIIa inhibitors in the clopidogrel and ticagrelor groups was monitored as another study end point, although the secondary safety end point evaluated was the incidence of bleeding events. RESULTS: Compared with the clopidogrel-treated group, ticagrelor treatment significantly reduced the incidence of MACCE [5 vs. 14; odds ratio (OR), 0.341; 95% confidence interval (CI), 0.120-0.964; P = 0.034] and the composite end points of cardiovascular death, nonfatal MI, and stroke (4 vs. 13; OR, 0.294; 95% CI, 0.094-0.916; P = 0.026). Fewer patients in the ticagrelor group received GPIIb/IIIa inhibitors after PPCI compared with those in the clopidogrel group (10 vs. 21; OR, 0.449; 95% CI, 0.206-0.979; P = 0.040). However, there were no significant differences between the groups in the incidences of all-cause mortality, nonfatal MI, unplanned revascularization, stroke, stent thrombosis (P = 0.522, P = 0.246, P = 0.246, P = 0.217, P = 0.246, respectively), or bleeding events (10 vs. 7; OR, 1.451; 95% CI, 0.541-3.891; P = 0.457). CONCLUSIONS: Among patients with STEMI undergoing PPCI, ticagrelor reduces the incidence of MACCE and the composite end point of cardiovascular death, nonfatal MI, and stroke compared with clopidogrel. Ticagrelor also reduces the need for GPIIb/IIIa inhibitors. However, no significant difference was observed in the risk of bleeding between the 2 groups.