The safety and prognostic evaluation of subsequent aortic surgery after thoracic endovascular aortic repair: a retrospective cohort study.

Background: Thoracic endovascular aortic repair (TEVAR) is a widely employed clinical procedure for treating various aortic pathologies. However, some patients require subsequent surgical interventions post-TEVAR, particularly due to life-threatening complications such as aortic dissection. This study aimed to evaluate the safety and prognosis associated with additional aortic surgeries following TEVAR. Methods: A retrospective analysis was conducted on 21 patients who underwent aortic surgery after TEVAR at Guangdong Provincial People's Hospital between September 2016 and August 2020. By compiling and reviewing perioperative data, we assessed surgical-related complications and survival rates. Results: Among the 21 patients, 95.2% were male, with an average age of 53 years. Preoperative comorbidities included hypertension in 15 individuals, abdominal aortic aneurysm in one patient, and coronary heart disease in two patients. The primary complications of TEVAR were stent leakage and retrograde aortic dissection, with the latter being the predominant type in subsequent aortic surgeries. The mean duration of aortic clamping during surgery was 130.0 minutes, with a deep hypothermic circulatory arrest time of 8.5 minutes. Postoperatively, two patients suffered in-hospital mortality, one developed renal dysfunction, four required re-entry into the operating room for further treatment, and the average length of hospital stay was 20 days. Following discharge, 14.3% of patients experienced complications, with central nervous system symptoms being the most prevalent. Kaplan-Meier survival analysis indicated a 5-year survival rate of 85.7%. Conclusions: Aortic surgical intervention following TEVAR is a safe therapeutic approach that can improve patient prognosis. However, meticulous management of the perioperative period is crucial for reducing the risk of complications and improving survival rates. This study provides valuable insights into aortic surgery post-TEVAR, but large-scale research is needed to validate these findings.

Molecular findings in patients for whole exome sequencing and mitochondrial genome assessment.

OBJECTIVE: Whole exome sequencing (WES) is becoming more widely used as a diagnostic tool in the field of medicine. In this article, we reported the diagnostic yield of WES and mitochondrial genome assessment in 2226 consecutive cases in a single clinical laboratory. MATERIALS AND METHODS: We retrospectively analyzed consecutive WES reports from 2226 patients with various genetic disorders. WES-process was focused exclusively on the probands and aimed at a higher diagnostic capacity. We determined the diagnostic rate of WES overall and by phenotypic category, mode of inheritance, mitochondrial genome variant, and copy number variants (CNVs). RESULTS: Among the 2226 patients who had diagnostic WES proband-only, the overall diagnostic yield of WES was 34.59% (770/2226). The highest diagnostic yield was observed in autosomal dominant disorders, at 45.58% (351/770), followed by autosomal recessive at 31.95%(246/770), X-linked disorder at 9.61%(74/770), and mitochondrial diseases at a notably lower 0.65%(5/770). The 12.21% (94/770) diagnoses were based on a total of 94 copy number variants reported from WES data. CNVs in children accounted for 67.02% of the total CNVs. While majority of the molecular diagnoses were related to nuclear genes, the inclusion of mitochondrial genome sequencing in the WES test contributed to five diagnoses. all mitochondrial diseases were identified in adults. CONCLUSIONS: The proband-only WES provided a definitive molecular diagnosis for 34.59% of a large cohort of patients while analysis of WES simultaneously analyzed the SNVs, exons, mitochondrial genome, and CNVs, thereby improving the diagnostic yield significantly compared to the single-detection WES method; and facilitating the identification of novel candidate genes.

Proximity hybridization based "turn-on" DNA tweezers for accurate and enzyme-free small extracellular vesicle analysis.

Small extracellular vesicles (sEVs) are a type of extracellular vesicle that carries many types of molecular information. The identification of sEVs is essential for the non-invasive detection and treatment of illnesses. Hence, there is a significant need for the development of simple, sensitive, and precise methods for sEV detection. Herein, a DNA tweezers-based assay utilizing a "turn-on" mechanism and proximity ligation was suggested for the efficient and rapid detection of sEVs through amplified fluorescence. The target facilitates the proximity combination of the C1 probe and C2 probe, resulting in the formation of a complete extended sequence. The elongated sequence can cyclically initiate the hairpin probe (HP), leading to the activation of DNA tweezers. An excellent linear correlation was achieved, with a limit of detection of 57 particles per µL. Furthermore, it has been effectively employed to analyze sEVs under intricate experimental conditions, demonstrating a promising and pragmatic prospect for future applications. Given that the identification of sEVs was successfully accomplished using a single-step method that exhibited exceptional sensitivity and strong resistance to interference, the proposed technique has the potential to provide a beneficial platform for accurate recognition of sEVs and early detection of diseases.

Incremental value of myocardial global longitudinal strain in predicting major adverse cardiac events among patients with hypertrophic cardiomyopathy.

OBJECTIVES: Endocardial global longitudinal strain (endo-GLS) measured with echocardiography (echo) has been demonstrated to be associated with myocardial fibrosis (MF) and is a prognostic predictor in patients with hypertrophic cardiomyopathy (HCM). Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging showed that MF is primarily located in the myocardial layer of the extremely hypertrophic septal or ventricular wall. We hypothesized that GLS of the myocardial layer (myo-GLS) is more strongly correlated with the extent of LGE (%LGE) and is a more powerful prognostic factor than endo-GLS. METHODS: A total of 177 inpatients (54.0 [IQR: 43.0, 64.0] years, female 37.3%) with HCM were retrospectively included from May 2019 to April 2021. Among them, 162 patients underwent echocardiographic examination and contrast-enhanced CMR within 7 days. Myo-GLS and %LGE were blindly assessed in a core laboratory. All the patients were followed after they were discharged. RESULTS: During a mean follow-up of 33.77 [IQR 30.05, 35.40] months, 14 participants (7.91%) experienced major adverse cardiac events (MACE). The MACE (+) group showed lower absolute endo-GLS and myo-GLS than the MACE (-) group. Myo-GLS was more associated with %LGE (r = -.68, P < .001) than endo-GLS (r = -.64, P < .001). Cox multivariable analysis indicated that absolute myo-GLS was independently associated with MACE (adjusted hazard ratio = .75, P < .05). Myo-GLS was better than endo-GLS at detecting MACE (+) patients (-8.64%, AUC .939 vs. - 16.375%, AUC .898, P < .05). CONCLUSIONS: Myo-GLS is a stronger predictor of MACE than endo-GLS in patients with HCM and is highly correlated with %LGE.

Dulaglutide restores endothelial progenitor cell levels in diabetic mice and mitigates high glucose-induced endothelial injury through SIRT1-mediated mitochondrial fission.

Type 2 diabetes mellitus (T2DM) significantly impairs the functionality and number of endothelial progenitor cells (EPCs) and resident endothelial cells, critical for vascular repair and regeneration, exacerbating the risk of vascular complications. GLP-1 receptor agonists, like dulaglutide, have emerged as promising therapeutic agents due to their multifaceted effects, including the enhancement of EPC activity and protection of endothelial cells. This study investigates dulaglutide's effects on peripheral blood levels of CD34+ and CD133+ cells in a mouse model of lower limb ischemia and its protective mechanisms against high-glucose-induced damage in endothelial cells. Results demonstrated that dulaglutide significantly improves blood flow, reduces tissue damage and inflammation in ischemic limbs, and enhances glycemic control. Furthermore, dulaglutide alleviated high-glucose-induced endothelial cell damage, evident from improved tube formation, reduced reactive oxygen species accumulation, and restored endothelial junction integrity. Mechanistically, dulaglutide mitigated mitochondrial fission in endothelial cells under high-glucose conditions, partly through maintaining SIRT1 expression, which is crucial for mitochondrial dynamics. This study reveals the potential of dulaglutide as a therapeutic option for vascular complications in T2DM patients, highlighting its role in improving endothelial function and mitochondrial integrity.

Physiological and molecular mechanisms of plant-root responses to iron toxicity.

The chemical form and physiological activity of iron (Fe) in soil are dependent on soil pH and redox potential (Eh), and Fe levels in soils are frequently elevated to the point of causing Fe toxicity in plants, with inhibition of normal physiological activities and of growth and development. In this review, we describe how iron toxicity triggers important physiological changes, including nitric-oxide (NO)-mediated potassium (K+) efflux at the tips of roots and accumulation of reactive oxygen species (ROS) and reactive nitrogen (RNS) in roots, resulting in physiological stress. We focus on the root system, as the first point of contact with Fe in soil, and describe the key processes engaged in Fe transport, distribution, binding, and other mechanisms that are drawn upon to defend against high-Fe stress. We describe the root-system regulation of key physiological processes and of morphological development through signaling substances such as ethylene, auxin, reactive oxygen species, and nitric oxide, and discuss gene-expression responses under high Fe. We especially focus on studies on the physiological and molecular mechanisms in rice and Arabidopsis under high Fe, hoping to provide a valuable theoretical basis for improving the ability of crop roots to adapt to soil Fe toxicity.

OsEIL1 is involved in the response to heterogeneous high ammonium in rice: A split-root analysis.

Ammonium (NH4+) concentrations in rice fields show heterogeneous spatial distribution under the combined influences of nitrogen fertilizer application and modern agronomic practices. However, the characteristics and mechanisms of rice roots in response to heterogeneous NH4+ supply are not well understood. Here, we found a systemic response of rice roots to heterogeneous and high (10 mM) NH4+ supply using a split-root experiment, and show root growth on the NH4+-free (NO3-) side was also inhibited by localized high-NH4+ supply. Moreover, OsEIL1 (encoding a core transcription factor in the ethylene signaling pathway) was found to be involved in the response of rice roots to heterogeneous NH4+. OsEIL1 mutation significantly increased the inhibitory effect of localized high-NH4+ on root growth of the NO3- side, as well as significantly increased NH4+ efflux there. Furthermore, our results indicate that the mitigating effect of OsEIL1 on NH4+ efflux is related to the regulated expression of OsVTC1-3 (encoding a GDP-mannose pyrophosphorylase). These findings provide insight into the mechanisms by which OsEIL1 responds to heterogeneous high NH4+ and contribute to our understanding of rice adaptation to heterogeneous NH4+ supply.

Plant iron status regulates ammonium-use efficiency through protein N-glycosylation.

Improving nitrogen-use efficiency is an important path toward enhancing crop yield and alleviating the environmental impacts of fertilizer use. Ammonium (NH4+) is the energetically preferred inorganic N source for plants. The interaction of NH4+ with other nutrients is a chief determinant of ammonium-use efficiency (AUE) and of the tipping point toward ammonium toxicity, but these interactions have remained ill-defined. Here, we report that iron (Fe) accumulation is a critical factor determining AUE and have identified a substance that can enhance AUE by manipulating Fe availability. Fe accumulation under NH4+ nutrition induces NH4+ efflux in the root system, reducing both growth and AUE in Arabidopsis (Arabidopsis thaliana). Low external availability of Fe and a low plant Fe status substantially enhance protein N-glycosylation through a Vitamin C1-independent pathway, thereby reducing NH4+ efflux to increase AUE during the vegetative stage in Arabidopsis under elevated NH4+ supply. We confirm the validity of the iron-ammonium interaction in the important crop species lettuce (Lactuca sativa). We further show that dolomite can act as an effective substrate to subdue Fe accumulation under NH4+ nutrition by reducing the expression of Low Phosphate Root 2 and acidification of the rhizosphere. Our findings present a strategy to improve AUE and reveal the underlying molecular-physiological mechanism.

Aortic size distribution among normal, hypertension, bicuspid, and Marfan populations.

Aims: Large-scale investigations on ascending aortic diameter, especially in the Asian population, are lacking. Furthermore, relevant evidence regarding the distribution of hypertension (HP), bicuspid aortic valve (BAV), and Marfan syndrome (MFS) is scarce. We aimed to examine the distribution of ascending aortic diameter in these populations in China. Methods and results: The data of a total number of 698 795 individuals who underwent cardiac ultrasound were subjected to retrospective analysis. After screening, 647 087 individuals were included in the final analysis. In the normal population, the mean ascending aortic diameter was 28.1 ± 3.2 mm (27.2 ± 3.1 mm in women vs. 29.0 ± 3.1 mm in men) (P < 0.001). Aortic diameter increased gradually with age (P < 0.001). The prevalence of aortic dilation, aneurysm, and dissection in individuals with HP was 12.83%, 2.70%, and 4.77%, respectively. In individuals with MFS, the corresponding rates were 43.92%, 35.31%, and 26.11%. Notably, although BAV patients had high incidences of aortic dilation (37.00%) and aortic aneurysm (16.46%), the incidence of aortic dissection was relatively low (0.74%). Most cases of aortic dissection occurred at an aortic diameter of less than 55 mm. However, in the overall population, the incidence of aortic dissection significantly increased with the increase in the aortic diameter, revealing the existence of an 'aortic paradox'. Conclusions: (i) The ascending diameter increases with age and is larger in men than in women; (ii) 'Aortic paradox' is explained; (iii) BAV bears a high rate of aortic dilation, but a low incidence of aortic dissection.

Three techniques of proximal root reconstruction and long term outcomes following repair of acute type A aortic dissection / 中国胸心血管外科临床杂志

@#Objective To compare the early and late outcomes of different techniques of proximal root reconstruction during the repair of acute type A aortic dissection, including aortic valve (AV) resuspension, isolated supracoronary ascending aorta replacement, and aortic root replacement procedure (Bentall). Methods All patients who underwent acute Type A aortic dissection repair between January 2010 and December 2015 in Fuwai Hospital were retrospectively analyzed in our study. There were 673 patients with 512 males and 161 females at mean age of 48.80±11.22 years. There were 403 patients as an AV resuspension group (287 males and 116 females at average age of 50.61±9.95 years), 95 patients as an isolated supracoronary ascending aorta replacement group (76 males and 19 females at average of 49.83±12.21 years), and 175 patients as an AV resuspension group (149 males and 26 females at average of 44.07±11.99 years). The differences of preoperative aortic insufficiency, intraoperative variables and postoperative aortic insufficiency were compared in the three groups. Results Five hundred ninety-one patients (87.8%) had aortic valve commissure involved. The proportion of mild degree, moderate degree, and severe degree among the three groups were statistically significant (31.7%, 52.4%, 15.9%; 87.4%, 12.6%, 0.0%; 23.4%, 56.0%, 20.6%; P < 0.01). The diameter of aortic sinus in the three groups was 39.06±5.11 mm, 38.27±4.41 mm, 50.39±6.22 mm, respectively, with a statistical difference ( P< 0.01). The duration of surgery, cardiopulmonary bypass time, aorta cross-clamp time were also statistically significant (P < 0.01). The in-hospital mortality was 11.73% in the whole group. There was no difference among the three groups (12.2% vs. 13.7% vs. 9.7%, P=0.58). Five-year survival rate was similar (83.06% vs. 81.27% vs. 83.05%, P=0.85). The 5-year free from over moderate aortic insufficiency rate were 95.2%, 98.6% and 100% respectively, with no statistical difference (P=0.07). There was no re-do operation for aortic root diseases in the whole group. Conclusion According to aortic root processing strategy in our center, AV resuspension, isolated supracoronary ascending aorta replacement, and aortic root replacement can achieve satisfactory results. However, there is higher incidence of aortic insufficiency through AV resuspension. Further study is needed to evaluate its efficacy.