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1.
J Cardiovasc Magn Reson ; 24(1): 4, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980199

RESUMO

BACKGROUND: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows quantification of biventricular blood flow by flow components and kinetic energy (KE) analyses. However, it remains unclear whether 4D flow parameters can predict cardiopulmonary exercise testing (CPET) as a clinical outcome in repaired tetralogy of Fallot (rTOF). Current study aimed to (1) compare 4D flow CMR parameters in rTOF with age- and gender-matched healthy controls, (2) investigate associations of 4D flow parameters with functional and volumetric right ventricular (RV) remodelling markers, and CPET outcome. METHODS: Sixty-three rTOF patients (14 paediatric, 49 adult; 30 ± 15 years; 29 M) and 63 age- and gender-matched healthy controls (14 paediatric, 49 adult; 31 ± 15 years) were prospectively recruited at four centers. All underwent cine and 4D flow CMR, and all adults performed standardized CPET same day or within one week of CMR. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes. Four flow components were analyzed: direct flow, retained inflow, delayed ejection flow and residual volume. Additionally, three phasic KE parameters normalized to end-diastolic volume (KEiEDV), were analyzed for both LV and RV: peak systolic, average systolic and peak E-wave. RESULTS: In comparisons of rTOF vs. healthy controls, median LV retained inflow (18% vs. 16%, P = 0.005) and median peak E-wave KEiEDV (34.9 µJ/ml vs. 29.2 µJ/ml, P = 0.006) were higher in rTOF; median RV direct flow was lower in rTOF (25% vs. 35%, P < 0.001); median RV delayed ejection flow (21% vs. 17%, P < 0.001) and residual volume (39% vs. 31%, P < 0.001) were both greater in rTOF. RV KEiEDV parameters were all higher in rTOF than healthy controls (all P < 0.001). On multivariate analysis, RV direct flow was an independent predictor of RV function and CPET outcome. RV direct flow and RV peak E-wave KEiEDV were independent predictors of RV remodelling index. CONCLUSIONS: In this multi-scanner multicenter 4D flow CMR study, reduced RV direct flow was independently associated with RV dysfunction, remodelling and, to a lesser extent, exercise intolerance in rTOF patients. This supports its utility as an imaging parameter for monitoring disease progression and therapeutic response in rTOF. Clinical Trial Registration https://www.clinicaltrials.gov . Unique identifier: NCT03217240.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35020259

RESUMO

Conventional square planar platinum complexes typically form one-dimensional assemblies as a result of unidirectional metallophilic and/or π···π intermolecular interactions. Organoplatinum(II) complexes with a cruciform shape are presented herein to construct two-dimensional (2D) microcrystals with full-color and white phosphorescence. These 2D crystals show unique monocomponent π···π stacking from either the cyclometalating or noncyclometalating ligand and the bicomponent alternate π···π stacking from both ligands along different facet directions. Anisotropic tri-directional waveguiding is further implemented on a single hexagonal microcrystal. These results demonstrate the great capability of organoplatinum(II) cruciform as a general platform to fabricate 2D phosphorescent micro-/nanocrystals for advanced photonic applications.

4.
Life Sci ; 289: 120231, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34921867

RESUMO

AIMS: To investigate the role of Skp2 and JunB on acute promyelocytic leukemia (APL) progression and the related mechanism. MATERIALS AND METHODS: The expression of Skp2 in NB4 cell line was depleted to explore its effect on proliferation and differentiation both in vitro and in vivo assays. Western blot and quantitative RT-PCR analysis were performed to explore Skp2-regulated downstream target genes. Luciferase and co-immunoprecipitation analysis indicated that PML-RARα inhibited the transactivation of JunB by interacting with the PU.1 protein. The western blot analysis confirmed that Skp2 could maintain the stability of PML-RARα. KEY FINDINGS: We report that the progression of APL and the attenuation of APL sensitivity to ATRA are positively associated with Skp2. Elevated Skp2 expression promotes APL progression by decreasing the expression of lncRNA HOTAIRM1 and inactivation of GSK3ß, causing autophagy inhibition followed by the suppression of PML-RARα ubiquitylation and degradation, which represses JunB transcriptional activation through PU.1/PML-RARα transcriptional complex to block cell differentiation. Coupled with ATRA or GSK3ß inhibitor treatment, genetic or pharmacological inhibition of Skp2 strikingly induces JunB expression by accelerating the degradation of PML-RARα, which contributes to the eradication of APL. Additionally, the expressions of Skp2 and JunB are negatively correlated in mice subcutaneous leukemia xenograft tumors. SIGNIFICANCE: Collectively, this study uncovers the roles of Skp2 in PML-RARα stabilization and in APL oncogenic functions. We reveal a novel mechanism of PML-RARα degradation and JunB regulation that constitute an important signaling network of Skp2-GSK3ß-PML/RARα-JunB.


Assuntos
Regulação Leucêmica da Expressão Gênica , Leucemia Promielocítica Aguda/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , Proteínas Quinases Associadas a Fase S/metabolismo , Fatores de Transcrição/biossíntese , Ativação Transcricional , Animais , Células HEK293 , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas de Fusão Oncogênica/genética , Estabilidade Proteica , Proteínas Quinases Associadas a Fase S/genética , Fatores de Transcrição/genética , Células U937 , Ensaios Antitumorais Modelo de Xenoenxerto
5.
J Mech Behav Biomed Mater ; 125: 104977, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34814078

RESUMO

Current generation of bioresorbable coronary scaffolds (BRS) posed thrombogenicity and deployment issues owing to its thick struts and overall profile. To this end, we hypothesize that the use of nanocomposite materials is able to provide improved material properties and sufficient radial strength for the intended application even at reduced strut thickness. The nanocomposite formulations of tantalum dioxide (Ta2O5), L-lactide functionalized (LA)-Ta2O5, hydroxyapatite (HA) and LA-HA with poly-l-lactic acid (PLLA) were evaluated in this study. Results showed that tensile modulus and strength were enhanced with non-functionalized nanofillers up until 15 wt% loading, whereas ductility was compromised. On the other hand, functionalized nanofillers/PLLA exhibited improved nanofiller dispersion which resulted higher tensile modulus, strength, and ductility. Selected nanocomposite formulations were evaluated using finite element analysis (FEA) of a stent with varying strut thickness (80, 100 and 150 µm). FEA data has shown that nanocomposite BRS with thinner struts (80-100 µm) made with 15 wt% LA-Ta2O5/PLLA and 10 wt% LA-HA/PLLA have increased radial strength, stiffness and reduced recoil compared to PLLA BRS at 150 µm. The reduced strut thickness can potentially mitigate issues such as scaffold thrombosis and promote re-endothelialisation of the vessel.


Assuntos
Implantes Absorvíveis , Nanopartículas , Análise de Elementos Finitos , Poliésteres , Stents
6.
Front Cardiovasc Med ; 8: 753918, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869663

RESUMO

Background: Arrhythmias are common cardiovascular complications in multiple myeloma (MM) patients and are related to a poor prognosis. Objective: This study aimed to assess the burden of arrhythmias and their prognostic value in patients with MM. Methods: This was a retrospective study of patients with MM between January 2015 and April 2020 at the First Affiliated Hospital of Xi'an Jiaotong University. The incidence of arrhythmia and associated risk factors were evaluated. The relationship between the type of arrhythmia and survival was analyzed. Results: A total of 319 patients with MM were identified, and 48.0% (153/319) had arrhythmias. The most common type of arrhythmia was sinus tachycardia (ST) (15.0%, 48/319), followed by sinus bradycardia (SB) (14.4%, 46/319), premature atrial contractions (PACs) (6.3%, 20/319), conduction disorders (CDs) (6.0%, 19/319), atrial fibrillation (AF) (6.0%, 19/319), premature ventricular contractions (PVCs) (4.4%, 14/319) and paroxysmal supraventricular tachycardia (PSVT) (0.6%, 2/319). The patients with arrhythmias had higher levels of log NT-proBNP and creatinine, greater bortezomib use, and a higher incidence of diabetes than those without arrhythmias (P < 0.05). The all-cause mortality rates of patients without arrhythmias and those with AF, ST, PACs, CDs, SB, and PVCs were 50.6% (84/166), 73.7% (14/19), 60.4% (29/48), 60.0% (12/20), 52.6% (10/19), 34.8% (16/46), and 28.6% (4/14), respectively. In a subgroup analysis of patients experiencing different types of arrhythmias, patients with SB had lower all-cause mortality than patients with AF (P < 0.01). Univariate and multivariate Cox analyses showed that there was a positive statistically significant association between SB and survival (HR: 0.592 [0.352-0.998], P = 0.049) in a subgroup analysis of different arrhythmias. Conclusions: Patients with MM had a heavy arrhythmia burden, and in this study, approximately half of MM patients had arrhythmias. MM patients with SB were associated with lower all-cause mortality than those with AF. SB might be an independent positive factor for prognosis.

7.
Int J Cardiol ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34864078

RESUMO

BACKGROUND: Physician visual assessment (PVA) in invasive coronary angiography (ICA) is the current clinical method to determine stenosis severity and guide percutaneous coronary intervention. This study sought to evaluate the effect of sex differences in assessing coronary stenosis severity between PVA and quantitative coronary angiography (QCA). METHODS: 209 patients with coronary artery disease (288 coronary lesions) underwent ICA and fractional flow reserve (FFR). ICA image processing including PVA and QCA was used to quantify diameter stenosis (DS). The difference of DS (ΔDS) between PVA and QCA was defined as DSPVA-DSQCA. DS ≥50% was considered anatomically obstructive. FFR ≤0.8 was defined as myocardial ischemia. RESULTS: Mean ±â€¯SD age was 63 ±â€¯9 years. There were no significant differences in DSPVA (61.1 ±â€¯16.3% vs 60.1 ±â€¯18.9%) and DSQCA (53.1 ±â€¯12.1% vs 55.4 ±â€¯14.3%) between females and males. However, ΔDS between PVA and QCA was higher in females (8.0 ±â€¯10.9%) than in males (4.7 ±â€¯10.9%) (P = 0.03). Thirty-four of 72 vessels (47.2%) in female patients and 75 of 216 vessels (34.7%) in male patients were classified differently by at least one grade using PVA compared to QCA assessment. DSPVA and DSQCA were negatively correlated with FFR in females (rPVA = -0.397, rQCA = -0.448) with an even stronger negative correlation in males (rPVA = -0.607, rQCA = -0.607). ROC analysis demonstrated that DSQCA myocardial ischemia (FFR ≤ 0.80) discrimination capability was superior to DSPVA in both sexes (P < 0.05). CONCLUSIONS: A systematic bias was found in PVA (QCA reference) for overestimating severity of coronary artery disease in females compared to males.

8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 3800-3803, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34892063

RESUMO

Coronary artery disease (CAD) is an important cause of morbidity and mortality. CT coronary angiography is considered as first-line of investigation in patients suspected of having CAD. Coronary artery centerline extraction is a challenging prerequisite for coronary artery stenosis evaluation. These challenges include the small and complex structure, variation of plaques and imaging noise. Deep learning methods often require adequate annotated data to build a good model. This work aims to adopt a dataset that has partial annotation to augment the data to train a Coronary Neural Network (CorNN) to track the coronary artery centerline. We combined a small training dataset with densely labelled centerline and radius, augmented with a larger dataset with only the centerline sparsely labelled to train networks to track centerlines from 3D computed tomography coronary angiography. The vessel orientation estimation is patch based, with or without additional radius prediction. The patch data are carefully positioned and sampled, which are tagged with the orientations computed based on the centerlines. Our experiment results show that, with the augmentation of the new data, although partially annotated, nearly 10% or more improvement has been achieved for the coronary artery extraction by the proposed approach.

9.
Heart Surg Forum ; 24(6): E1023-E1026, 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34962466

RESUMO

BACKGROUND: Cardiac paragangliomas are rare neuroendocrine tumors that will cause significant morbidity if left undiagnosed. Because of the paucity of cohort data, their rapid diagnosis and appropriate management still pose unique challenges to cardiac surgeons. We aimed to investigate the clinical features and surgical management of primary cardiac paragangliomas in our single center. METHODS: From May 2014 to October 2020, patients diagnosed with primary cardiac paragangliomas retrospectively were reviewed. Demographic data, clinical presentation, preoperative imaging methods, surgical resection, perioperative management, histological analysis, and outcomes were recorded. Postoperative follow up also was reviewed. RESULTS: With multiple imaging methods, including echocardiography, computed tomography, positron-emission tomographic-computed tomography, and biochemical tests, there were five cases of primary cardiac paraganglioma verified by postoperative immunohistochemical staining, two of which were hormonally active. There were no metastatic cardiac paragangliomas, according to positron-emission tomographic-computed tomography, and all patients accepted surgical treatment. Preoperative adrenoceptor blockade was given to hormonally active patients, accordingly. Complete resection of the tumor was accomplished under cardiopulmonary bypass in each case. Tumor distribution included two masses on the roof of the left atrium, two masses in the right atrioventricular groove, and one between the ascending aorta and main pulmonary artery. Immunohistochemical staining for chromogranin, neuron-specific enolase, synaptophysin, and S-100 were positive, which were typical of cardiac paraganglioma. There were no operative deaths. All the patients had an uneventful recovery except one patient who underwent low cardiac output syndrome. During follow up (mean 4.2 years, range 0.6-7.0 years), all patients were well with New York Heart Association class I or II. Only one patient developed thyroid carcinoma three years after surgery but with no paraganglioma recurrence during periodic computed tomography, and this patient recovered well after thyroidectomy. CONCLUSION: Although cardiac paragangliomas are rare and may present surgical challenges for clinicians, surgical resection remains the choice of treatment with favorable outcomes through a multidisciplinary heart team. Moreover, lifelong surveillance still is recommended to detect possible recurrence or associated nonchromaffin tumors in time.

10.
Chin J Nat Med ; 19(12): 921-929, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34961590

RESUMO

This work was aimed to establish a quality control method for evaluating the effects on glucose and lipids of the fruiting body of Isaria cicadae Miquel from strain Ic-17-7 (Ic-17-7fb) using a rat model of type 2 diabetes (T2DM). Random amplified polymorphic DNA, sequence-characterized amplified region, and high-performance liquid chromatography (HPLC) were used for the quality control of Ic-17-7fb. The pharmacological effects on streptozocin (STZ)-induced high fat diet (HFD)-fed Albino Wistar rats were evaluated. The rats underwent the following treatments: control, metformin, Ic-17-7fb (0.166 and 0.5 g·kg-1) or without treatment. The fasting blood glucose (FBG), blood glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-c), and low-density lipoprotein (LDL-c) were measured. Ic-17-7fb amplified a single specific band by S11-2-F3 and S11-2-R3 primers. An HPLC-based quality and quantity method was established for industrial application. The contents of adenosine and N6-(2-hydroxyethyl) adenosine (HEA) of the cultivated Ic-17-7fb were analyzed. All of the validation lots of cultured Ic-17-7fb passed the quantity control of the training set (0.90 mg·g-1 of adenosine and 0.89 mg·g-1 of HEA). After two weeks of administration, the average FBG was 4.89 ± 0.42 (control), 26.10 ± 5.77 (model), 23.63 ± 6.15 (metformin), 17.96 ± 9.36 (Ic-17-7fb for 0.166 g·kg-1), and 19.69 ± 8.71 mmol·L-1 (Ic-17-7fb for 0.5 g·kg-1). The FBG of Ic-17-7fb (0.166 g·kg-1) treatment significantly reduced by 31.19%, compared with the model after two weeks of administration (P < 0.01). Metformin, Ic-17-7fb (0.166 g·kg -1), and Ic-17-7fb (0.5 g·kg-1) reduced TC, TG, HDL-c, and LDL-c compared with the T2DM model treatment at the 6th week of treatment (P < 0.05). This study established the first quality standard for Ic-17-7fb, which can be effectively applied in the treatment of T2DM. The reliable quality control method and pharmacological effect will broaden its application space.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Animais , Glicemia , Cordyceps , Diabetes Mellitus Tipo 2/tratamento farmacológico , Controle de Qualidade , Ratos , Ratos Wistar
11.
Front Cardiovasc Med ; 8: 739633, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746257

RESUMO

The aim of this study was to evaluate a new analytical method for calculating non-invasive fractional flow reserve (FFRAM) to diagnose ischemic coronary lesions. Patients with suspected or known coronary artery disease (CAD) who underwent computed tomography coronary angiography (CTCA) and invasive coronary angiography (ICA) with FFR measurements from two sites were prospectively recruited. Obstructive CAD was defined as diameter stenosis (DS) ≥50% on CTCA or ICA. FFRAM was derived from CTCA images and anatomical features using analytical method and was compared with computational fluid dynamics (CFD)-based FFR (FFRB) and invasive ICA-based FFR. FFRAM, FFRB, and invasive FFR ≤ 0.80 defined ischemia. A total of 108 participants (mean age 60, range: 30-83 years, 75% men) with 169 stenosed coronary arteries were analyzed. The per-vessel accuracy, sensitivity, specificity, and positive predictive and negative predictive values were, respectively, 81, 75, 86, 81, and 82% for FFRAM and 87, 88, 86, 83, and 90% for FFRB. The area under the receiver operating characteristics curve for FFRAM (0.89 and 0.87) and FFRB (0.90 and 0.86) were higher than both CTCA- and ICA-derived DS (all p < 0.0001) on per-vessel and per-patient bases for discriminating ischemic lesions. The computational time for FFRAM was much shorter than FFRB (2.2 ± 0.9 min vs. 48 ± 36 min, excluding image acquisition and segmentation). FFRAM calculated from a novel and expeditious non-CFD approach possesses a comparable diagnostic performance to CFD-derived FFRB, with a significantly shorter computational time.

12.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(11): 987-995, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34809738

RESUMO

Objective To investigate the effect of lncRNA CRNDE on proliferation, apoptosis, and cell cycle of U937 cells and its mechanism. Methods The expression level of CRNDE in bone marrow cells of AML patients was analyzed by GEPIA database; the mRNA expression levels of miR-136-5p, CRNDE, and minichromosome maintenance 5(MCM5) in AML cell lines were detected by quantitative real-time PCR (qRT-PCR). The lentiviral vector with CRNDE knocked down was constructed and transfected into U937 cells which were randomized into CRNDE knockdown group (sh-CRNDE group) and negative control group (sh-NC group); miR-136-5p mimic and miR-136-5p inhibitor were transfected respectively to overexpress and knock down miR-136-5p in U937 cells which were randomized into miR-136-5p-mimic group, NC-mimic group, miR-136-5p-inhibitor group, and NC-inhibitor group. The effect of CRNDE and miR-136-5p on proliferation was detected by CCK-8 assay and cell counting assay, and the effect of them on cell cycle and apoptosis was detected by flow cytometry. The mRNA expressions of miR-136-5p, CRNDE, and MCM5 were detected by qRT-PCR, and the protein expressions of MCM5, Bcl2, cyclin D1, and cyclin A2 were detected by Western blotting. Results CRNDE was highly expressed in the bone marrow and cell lines of AML patients. Knockdown of CRNDE upregulated miR-136-5p, inhibited the MCM5 mRNA and protein expressions and the cell proliferation, promoted the cell apoptosis, and blocked the cell cycle in G1 phase. Overexpression of miR-136-5p also inhibited the expression of MCM5 at both mRNA and protein levels, while knockdown of miR-136-5p reversed those effects. Conclusion CRNDE promotes the proliferation and inhibits the apoptosis of U937 cells by downregulating miR-136-5p and upregulating MCM5.


Assuntos
MicroRNAs , RNA Longo não Codificante , Apoptose/genética , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , MicroRNAs/genética , Células U937
13.
Zhongguo Gu Shang ; 34(10): 901-5, 2021 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-34726015

RESUMO

OBJECTIVE: To explore the effect of metabolic syndrome on 15 days postoperative adverse events of femoral intertrochanteric fractures with internal fixation. METHODS: From January 2011 to June 2019, 986 elderly patients with intertrochanteric fracture were treated with internal fixation, including 312 males and 674 females, with an average age of(77.71± 7.58) years old. And there were 97 patients with metabolic syndrome and 889 patients without metabolic syndrome. Through the electronic medical record system, the patient's age, gender, fracture type, cause of trauma, body mass index, smoking history, preoperative comorbidities, preoperative bloodtransfusion, operation timing, ASA classification, anesthesia method, internal fixation type, operation duration, and 15 days postoperative adverse events, which include surgical site infection, acute heart failure, acute respiratory failure, pulmonary infection, acute renal failure, DVT, embolism in important organs, urinary tract infection, death, and blood transfusion after surgery were collected. The differences of preoperative and intraoperative baseline datas and 15 days postoperative adverse events between the two groups were compared and analyzed by t text or univariate χ2 test. Adjusted for the preoperative and intraoperative mixed factors with P<0.05, and 15 days postoperative adverse events with P<0.05 were then analyzed by multivariate unconditional Logistic regression analysis to further study the independent effects of metabolic syndrome on 15 days postoperative adverse events. RESULTS: There were statistical differences in age, body mass index, history of cardiac insufficiency, history of COPD, history of renal insufficiency, operation timing, ASA classification, operation duration, surgical site infection, acute heart failure, DVT, urinary tract infection and blood transfusion between two groups (P<0.05). Adjusted for the preoperative and intraoperative mixed factors, multivariate unconditional logistic regression analysis showed that metabolic syndrome could increase the infection rate of the surgical site [OR=3.785, 95%CI (1.086-13.188), P= 0.037], DVT incidence rate[OR=2.265, 95%CI(1.096-4.682), P=0.027], urinary tract infection rate[OR=2.703, 95%CI (1.049-6.963), P=0.0390], and blood transfusion rate [OR=1.811, 95%CI (1.142-2.870), P=0.012]. CONCLUSION: Elderly patients with intertrochanteric fracture with metabolic syndrome had higher postoperative surgical site infection rate, DVT incidence rate, urinary tract infection rate, and postoperative blood transfusion rate. Therefore, the orthopedic treatment team should give more attentionand optimize the treatment plan during the perioperative period with the cooperation of internal physician and anesthesiologist.


Assuntos
Fixação Intramedular de Fraturas , Fraturas do Quadril , Síndrome Metabólica , Idoso , Idoso de 80 Anos ou mais , Pinos Ortopédicos , Feminino , Fixação Interna de Fraturas/efeitos adversos , Fixação Intramedular de Fraturas/efeitos adversos , Fraturas do Quadril/cirurgia , Humanos , Masculino , Síndrome Metabólica/complicações , Estudos Retrospectivos , Resultado do Tratamento
14.
J Cardiovasc Magn Reson ; 23(1): 105, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34615541

RESUMO

BACKGROUND: Relationships between right ventricular (RV) and left ventricular (LV) shape and function may be useful in determining optimal timing for pulmonary valve replacement in patients with repaired tetralogy of Fallot (rTOF). However, these are multivariate and difficult to quantify. We aimed to quantify variations in biventricular shape associated with pulmonary regurgitant volume (PRV) in rTOF using a biventricular atlas. METHODS: In this cross-sectional retrospective study, a biventricular shape model was customized to cardiovascular magnetic resonance (CMR) images from 88 rTOF patients (median age 16, inter-quartile range 11.8-24.3 years). Morphometric scores quantifying biventricular shape at end-diastole and end-systole were computed using principal component analysis. Multivariate linear regression was used to quantify biventricular shape associations with PRV, corrected for age, sex, height, and weight. Regional associations were confirmed by univariate correlations with distances and angles computed from the models, as well as global systolic strains computed from changes in arc length from end-diastole to end-systole. RESULTS: PRV was significantly associated with 5 biventricular morphometric scores, independent of covariates, and accounted for 12.3% of total shape variation (p < 0.05). Increasing PRV was associated with RV dilation and basal bulging, in conjunction with decreased LV septal-lateral dimension (LV flattening) and systolic septal motion towards the RV (all p < 0.05). Increased global RV radial, longitudinal, circumferential and LV radial systolic strains were significantly associated with increased PRV (all p < 0.05). CONCLUSION: A biventricular atlas of rTOF patients quantified multivariate relationships between left-right ventricular morphometry and wall motion with pulmonary regurgitation. Regional RV dilation, LV reduction, LV septal-lateral flattening and increased RV strain were all associated with increased pulmonary regurgitant volume. Morphometric scores provide simple metrics linking mechanisms for structural and functional alteration with important clinical indices.


Assuntos
Insuficiência da Valva Pulmonar , Tetralogia de Fallot , Adolescente , Adulto , Criança , Estudos Transversais , Humanos , Valor Preditivo dos Testes , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/etiologia , Estudos Retrospectivos , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/cirurgia , Função Ventricular Direita , Adulto Jovem
15.
Angew Chem Int Ed Engl ; 60(51): 26710-26717, 2021 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-34606167

RESUMO

The intermolecular asymmetric radical oxidative C(sp3 )-C(sp) cross-coupling of C(sp3 )-H bonds with readily available terminal alkynes is a promising method to forge chiral C(sp3 )-C(sp) bonds because of the high atom and step economy, but remains underexplored. Here, we report a copper-catalyzed asymmetric C(sp3 )-C(sp) cross-coupling of (hetero)benzylic and (cyclic)allylic C-H bonds with terminal alkynes that occurs with high to excellent enantioselectivity. Critical to the success is the rational design of chiral oxazoline-derived N,N,P(O)-ligands that not only tolerate the strong oxidative conditions which are requisite for intermolecular hydrogen atom abstraction (HAA) processes but also induce the challenging enantiocontrol. Direct access to a range of synthetically useful chiral benzylic alkynes and 1,4-enynes, high site-selectivity among similar C(sp3 )-H bonds, and facile synthesis of enantioenriched medicinally relevant compounds make this approach very attractive.

16.
World J Clin Cases ; 9(27): 8114-8119, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34621869

RESUMO

BACKGROUND: Empyema is a severe complication following pneumonectomy that is associated with high morbidity and mortality rates. Although there are a wide variety of treatment options, successful management remains challenging when this condition is combined with a large cavity in very thin patients who had previously undergone a posterolateral thoracotomy. CASE SUMMARY: We reported the case of a thin, 63-year-old man with a progressive pulmonary cyst who underwent left pneumonectomy via posterolateral thoracotomy 23 years ago. After an initially uneventful postoperative course, he was readmitted with empyema and a large cavity 21 years after surgery. He was successfully treated with limited thoracoplasty, followed by free vastus lateralis musculocutaneous flap transposition. CONCLUSION: This case highlights that the treatment mode of limited thoracoplasty and free vastus lateralis musculocutaneous flap transposition is safe and effective for the management of postpneumonectomy empyema with a large cavity in thin patients who had previously undergone a posterolateral thoracotomy.

17.
J Med Chem ; 64(21): 15582-15592, 2021 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-34623802

RESUMO

The "inverse drug discovery" strategy is a potent means of exploring the cellular targets of latent electrophiles not typically used in medicinal chemistry. Cyclopropenone, a powerful electrophile, is generally used in bio-orthogonal reactions mediated by triarylphosphine or in photo-triggered cycloaddition reactions. Here, we have studied, for the first time, the proteome reactivity of cyclopropenones in live cells and discovered that the cyclopropenone warhead can specifically and efficiently modify a triple-negative breast cancer driver, glutathione S-transferase pi-1 (GSTP1), by covalently binding at the catalytic active site. Further structure optimization and signaling pathway validation have led to the discovery of potent inhibitors of GSTP1.

18.
Fish Physiol Biochem ; 47(6): 1951-1967, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34633578

RESUMO

At present, due to the influence of global warming, seasonal change, diurnal variation, and eutrophication of the water body, hypoxia has become one of the major factors limiting the stable development of cobia (Rachycentron canadum) culture. In this study, the miRNAs involved in hypoxia stress were screened, and the target genes of miRNAs were annotated and analyzed. The results showed that a total of 184 conservative microRNA (miRNA) and 121 newly predicted miRNA were obtained by sequencing the liver of control (C) and hypoxic (dissolved oxygen, DO (2.64 ± 0.25) mg/L; 3 h) (S) groups. The pathways involved in energy metabolism included starch and sucrose metabolism (ko00500), glycosaminoglycan degradation (ko00531), and galactose metabolism (ko00052). The results indicate that the body maintains physiological activities by regulating some important pathways at the transcriptional level under hypoxia stress, such as the conversion of aerobic metabolism and anaerobic metabolism, the reduction of energy consumption, and the promotion of red blood cell proliferation to maintain the homeostasis of the body.

19.
Nat Commun ; 12(1): 5969, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645811

RESUMO

The Yersinia outer protein J (YopJ) family effectors are widely deployed through the type III secretion system by both plant and animal pathogens. As non-canonical acetyltransferases, the enzymatic activities of YopJ family effectors are allosterically activated by the eukaryote-specific ligand inositol hexaphosphate (InsP6). However, the underpinning molecular mechanism remains undefined. Here we present the crystal structure of apo-PopP2, a YopJ family member secreted by the plant pathogen Ralstonia solanacearum. Structural comparison of apo-PopP2 with the InsP6-bound PopP2 reveals a substantial conformational readjustment centered in the substrate-binding site. Combining biochemical and computational analyses, we further identify a mechanism by which the association of InsP6 with PopP2 induces an α-helix-to-ß-strand transition in the catalytic core, resulting in stabilization of the substrate recognition helix in the target protein binding site. Together, our study uncovers the molecular basis governing InsP6-mediated allosteric regulation of YopJ family acetyltransferases and further expands the paradigm of fold-switching proteins.


Assuntos
Acetiltransferases/química , Apoproteínas/química , Arabidopsis/microbiologia , Proteínas de Bactérias/química , Ácido Fítico/química , Ralstonia solanacearum/química , Acetiltransferases/genética , Acetiltransferases/metabolismo , Regulação Alostérica , Apoproteínas/genética , Apoproteínas/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Domínio Catalítico , Clonagem Molecular , Cristalografia por Raios X , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Modelos Moleculares , Ácido Fítico/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Ralstonia solanacearum/enzimologia , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Especificidade por Substrato , Tabaco/microbiologia
20.
BMC Cardiovasc Disord ; 21(1): 473, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598676

RESUMO

BACKGROUND: Trimetazidine (TMZ) pretreatment protects cardiomyocytes during cardiac surgery. TMZ may protect elderly patients with ischaemic heart disease (IHD) undergoing non-cardiac surgery. METHODS: This was a randomized, double-blind, placebo-controlled trial (registration #ChiCTR1900025018) of patients with IHD scheduled to undergo non-cardiac surgery at Shenzhen People's Hospital (Shenzhen, Guangdong Province, China) between June 2014 and September 2015, randomized to 60 mg TMZ or placebo 12 h before surgery. The primary endpoint was the occurrence of in-hospital cardiovascular events. The secondary endpoints were myocardial ischaemia on five-lead electrocardiogram (cECG), cardiac troponin I (cTnI) elevation, cardiac death, acute coronary events, heart failure, and arrhythmia requiring treatments. RESULTS: Compared with the placebo group, the TMZ group showed a lower occurrence of in-hospital cardiovascular events (primary endpoint, 20.0% vs. 37.5%, P = 0.02), myocardial ischaemia (15.0% vs. 32.5%, P < 0.01), cTnI elevation (2.5% vs. 10%, P < 0.01), acute coronary events (10.0% vs. 20.0%, P < 0.05), heart failure (0% vs. 2.5%, P < 0.05), and arrhythmia requiring treatment (17.5% vs. 35.0%, P < 0.05). There was no acute myocardial infarction during the 30-day postoperative period. CONCLUSIONS: In elderly patients with IHD undergoing non-cardiac surgery, TMZ pretreatment was associated with myocardial protective effects. Trial registration The trial was prospectively registered at http://www.chictr.org.cn/showproj.aspx?proj=41909 with registration number [ChiCTR1900025018] (7/8/2019).

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