Identification of genes associated with fatty acid biosynthesis based on 214 safflower core germplasm.

BACKGROUND: Safflower (Carthamus tinctorius L.) is an oilseed crop with substantial medicinal and economic value. However, the methods for constructing safflower core germplasm resources are limited, and the molecular mechanisms of lipid biosynthesis in safflower seeds are not well understood. RESULTS: In this study, 11 oil-related quantitative traits and 50 pairs of InDel markers were used to assess the diversity of a collection of 605 safflower germplasms. The original safflower germplasm exhibited rich phenotypic diversity, with high variation for most of the phenotypic traits under investigation. Similarly, high genetic diversity was evaluated in the original germplasm, in which the mean Shannon's information index (I), observed heterozygosity (H0), and expected heterozygosity (He) were 0.553, 0.182, and 0.374, respectively. Four subgroups with strong genetic structures were identified and a core germplasm of 214 cultivars was constructed, which is well represented in the original germplasm. Meanwhile, differential expression analysis of the transcriptomes of high and low linoleic acid safflower varieties at two stages of seed development identified a total of 47 genes associated with lipid biosynthesis. High expression of the genes KAS II and SAD enhanced the synthesis and accumulation of oleic acid, while FAD genes like FAD2 (Chr8G0104100), FAD3, FAD7 and FAD8 promoted the consumption of oleic acid conversion. The coordinated regulation of these multiple genes ensures the high accumulation of oleic acid in safflower seed oil. CONCLUSIONS: Based on these findings, a core germplasm of 214 cultivars was constructed and 47 candidate genes related to unsaturated fatty acid biosynthesis and lipid accumulation were identified. These results not only provide guidance for further studies to elucidate the molecular basis of oil lipid accumulation in safflower seeds, but also contribute to safflower cultivar improvements.

Predicting New-Onset Postoperative Atrial Fibrillation Following Isolated Coronary Artery Bypass Grafting: Development and Validation of a Novel Nomogram.

OBJECTIVE: To select variables associated with new-onset postoperative atrial fibrillation (POAF) following isolated coronary artery bypass grafting (CABG) and develop a nomogram for risk prediction in a Chinese population. METHODS: The study retrospectively enrolled 4854 consecutive patients undergoing isolated CABG from February 2018 to September 2019, they were divided into derivation cohort and validation cohort with a 3:1 ratio according to the order of operation date. In the derivation cohort, significant variables were selected by use of the multivariate logistic backward stepwise regression analysis and a nomogram model was built on the strength of the results. The model performance was assessed in terms of discrimination and calibration. Besides, we compared the discriminative ability for POAF of the nomogram with established prediction models (CHA2DS2-VASc and HATCH scores) in the two cohorts. RESULTS: POAF occurred in 1025 (28.2%) out of 3641 patients in the derivation cohort, and in 337 (27.8%) out of 1213 patients in the validation cohort. A nomogram, composed of eight prognostic variables, namely age, sex, heart rate, hypertension, left ventricular ejection fraction (LVEF) <50%, left atrial diameter (LAD) > 40mm, estimated glomerular filtration rate (eGFR) level, and on-pump surgery, was constructed from the derivation cohort. The nomogram had substantial discriminative ability in derivation and validation cohorts with the area under the receiver operating characteristic curves (AUCs) of 0.661 (95% confidence interval, 0.642-0.681) and 0.665 (95% confidence interval, 0.631-0.699), respectively, and showed well-fitted calibration curves. Compared with CHA2DS2-VASc, HATCH and POAF scores, respectively, the nomogram had superior discrimination performance. CONCLUSION: We constructed a novel nomogram with improved accuracy for predicting the risk of POAF following isolated CABG, which might help clinicians predict individual probability of POAF and achieve effective prophylaxis.

Association Between Triglyceride-Glucose Index and 2-Year Adverse Cardiovascular and Cerebrovascular Events in Patients with Type 2 Diabetes Mellitus Who Underwent Off-Pump Coronary Artery Bypass Grafting.

BACKGROUND: Data on the relationship between the triglyceride glucose (TyG) index and prognosis after off-pump coronary artery bypass grafting (OPCABG) are limited. This retrospective observational cohort study evaluated the association of the TyG index with prognosis in patients with diabetes mellitus who underwent OPCABG. METHODS: The TyG index was calculated using the following equation: TyG index = ln (fasting triglyceride level [mg/dL] × fasting glucose level [mg/dL]/2). The primary outcomes included the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs), which were defined as all-cause death, nonfatal myocardial infarction, nonfatal stroke and symptomatic graft failure. The association between the TyG index and MACCEs was assessed by Cox proportional hazards regression analysis. RESULTS: A total of 1578 patients with diabetes who underwent OPCABG (mean age, 62.9 ± 8.0 years; men, 72.7%) were enrolled in this study. Over the follow-up of 2 years, 176 patients (11.2%) had at least 1 primary endpoint event. The follow-up incidence of the primary endpoint rose with increasing TyG index tertiles. The multivariate Cox proportional hazards regression analysis adjusted for multiple confounders revealed a hazard ratio for the primary endpoint of 2.133 (95% CI 1.347-3.377; P for trend = 0.001) when the highest and lowest TyG index tertiles were compared. CONCLUSION: The TyG index was significantly and positively associated with MACCEs, suggesting that the TyG index may be a valuable predictor of adverse cardiovascular and cerebrovascular outcomes after OPCABG in patients with T2DM.

The effects of high-sensitivity C-reactive protein on the clinical outcomes in obstructive sleep apnea patients undergoing off-pump coronary artery bypass grafting.

PURPOSE: To investigate the relationship between obstructive sleep apnea (OSA) severity and high-sensitivity C-reactive protein (Hs-CRP), and their respective impact on the clinical outcomes in patients undergoing off-pump cardiac artery bypass grafting (OPCABG). METHODS: We enrolled consecutive eligible patients listed for elective OPCABG who underwent cardiorespiratory polygraphy before surgery between January 2019 and December 2019 in this prospective observational single-center study. Baseline, intraoperative, and postoperative clinical data were compared between absent-mild and moderate-severe OSA groups. Regression analysis investigated the relationship between Hs-CRP level and severity of OSA, and further assessed the factors influencing postoperative atrial fibrillation, duration of hospitalization, and hospital cost. RESULTS: Patients with moderate-severe OSA accounted for 42.3% (52/123) of the cohort. Partial pressure of carbon dioxide (PCO2), Hs-CRP, apnea hypopnea index (AHI), mean apnea time, maximum apnea time, and oxygen desaturation index ODI ≥ 3% were significantly higher in the moderate-severe OSA group than in the absent-mild OSA group. Left ventricle ejection fraction (LVEF), lowest arterial oxygen saturation (SaO2), and mean SaO2 were significantly lower in the moderate-severe OSA group. Moderate-severe OSA was associated with elevated Hs-CRP level (OR = 2.356, 95% CI 1.101-5.041, P = 0.027). Hs-CRP was an independent risk factor for post-CABG atrial fibrillation (POAF) (OR = 1.212, P = 0.01). Hs-CRP level independently correlated with duration of hospitalization (B = 0.456, P = 0.001) and hospital cost (B = 1.111, P = 0.044). CONCLUSION: Hs-CRP level was closely related to OSA severity and have potential utility in predicting POAF, duration of hospitalization, and hospital costs in patients undergoing OPCABG.

Obstructive Sleep Apnea Increases the Risk of Perioperative Myocardial Infarction Following Off-Pump Coronary Artery Bypass Grafting.

Background and Aims: The impact of obstructive sleep apnea (OSA) on perioperative myocardial infarction (PMI) following coronary artery bypass grafting (CABG) remains unclear. Off-pump CABG (OPCABG) has become a common practice for CABG in China. The present study investigated mainly the correlation between OSA and PMI following OPCABG. Methods: In this prospective observational single-center study, consecutive eligible patients listed for elective OPCABG underwent cardiorespiratory polygraphy before surgery between January 2019 and June 2020. OSA was defined as an apnea-hypopnea index (AHI) ≥15 events/h. The primary end point was perioperative myocardial infarction (PMI) following OPCABG (type 5 MI). Results: Patients with OSA accounted for 42.2% (62/147) of the cohort. Twenty-four patients (16.3%) met the protocol criteria for PMI: 17 (27.4%) in the OSA group and 7 (8.2%) in the non-OSA group (P = 0.002). Multivariate logistic regression analysis revealed that AHI (OR = 1.115, 95% CI 1.066 to 1.166, P < 0.001), high-sensitivity c-reactive protein (hs-CRP) (OR = 1.080, 95% CI 1.025 to 1.138, P = 0.004), and SYNTAX score (OR = 1.098, 95% CI 1.056 to 1.141, P < 0.001) were associated with PMI incidence. Furthermore, ROC analysis revealed that the AHI (AUC = 0.766, 95% CI 0.689 to 0.832, P < 0.001) and SYNTAX score (AUC = 0.789, 95% CI 0.715 to 0.852, P < 0.001) had predictive value for PMI. In addition, multiple linear regression analysis showed that the AHI was an independent influencing factor of hs-CRP (B = 0.176, 95% CI 0.090 to 0.263, P < 0.001) and the SYNTAX score (B = 0.553, 95% CI 0.397 to 0.709, P < 0.001). Conclusions: OSA was independently associated with a higher incidence of PMI following OPCABG, and the formation of severe coronary atherosclerotic lesions aggravated by an enhanced inflammatory response might be the potential mechanism. The efficacy of CPAP treatment for improving prognosis after CABG remains to be further investigated.

Case Report: Cardiac Surgery and Combined Lipid-Lowering Drug Therapy for Homozygous Familial Hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH) is a rare, autosomal dominant, hereditary, metabolic disease. HoFH patients exhibit severe coronary stenosis and valvular disease, which may result in sudden death, even during adolescence. The challenges faced during surgery and the poor curative effect of conventional lipid-lowering therapy create a treatment bottleneck. We report a rare case of HoFH in a 12-years-old boy with acute myocardial infarction, severe mitral insufficiency, and moderate aortic insufficiency. Coronary artery bypass grafting and valvuloplasty resulted in improved heart function. Postoperative combined lipid-lowering drug therapy was able to reduce low-density lipoprotein cholesterol level from 15.37 mm/L to 6.41 mmol/L. Thus, the combination of medical and surgical treatment was considered effective and can be used to inform treatment guidelines for HoFH with severe complications.

Epigallocatechin gallate attenuates mitochondrial DNA-induced inflammatory damage in the development of ventilator-induced lung injury.

OBJECTIVE: We aim to investigate the role of mitochondrial DNA (mtDNA), a novel endogenous pro-inflammatory cytokine, in the development of ventilator-induced lung injury (VILI). Moreover, the protective effect of epigallocatechin gallate (EGCG) on VILI through inhibiting local mtDNA release was examined. METHODS: From March 2015 to March 2016, bronchoalveolar lavage fluid (BALF) from 36 patients with VILI and well-matched 36 patients without VILI after major surgery were consecutively collected. The expression levels of mtDNA and inflammatory cytokines in BALF were tested. SD rats were divided into five groups: control, low tidal volume (7 ml/kg) group, high tidal volume (HTV, 40 ml/kg) group, HTV+low dose EGCG and HTV+high dose EGCG groups. BALF were collected to examine the expression levels of mtDNA and several inflammatory cytokines and the lung tissue was harvested for pathological examinations. In addition, cyclic stretch cell culture was used and culture media was collected to analyze expressions of inflammatory cytokines. Administration of mtDNA in a rat model and in vitro cell culturing were used to confirm its pro-inflammatory properties in the development of inflammatory lung injury. RESULTS: A Significant elevation of mtDNA was detected in BALF from patients with VILI (581 ±â€¯193 vs. 311 ±â€¯137, p < 0.05) and also in rats ventilated with HTV. EGCG could significantly inhibit HTV-induced local mtDNA release and attenuate the level of inflammatory lung injuries (reduced infiltration of local inflammatory cells, lower lung wet/dry ratio and expression levels of inflammatory cytokines). The beneficial effects of EGCG on preventing inflammatory lung injuries were in a concentration-dependent manner. Meanwhile, higher expression levels of mtDNA and inflammatory cytokines were observed in the media of cyclic stretched cell culture compared to those in the control group (p < 0.05). Furthermore, intra-tracheal administration of mtDNA in rats could lead to a marked increase of local inflammatory cytokines and subsequent inflammatory lung injuries (p < 0.05). And by adding mtDNA into the cell culture, higher level of inflammatory cytokines in the media was detected (p < 0.05). EGCG also showed preventive effects on inflammatory responses on a concentration-dependent manner (p < 0.05). CONCLUSION: The increased expression level of mtDNA and subsequent inflammatory cytokines overproduction may play an important role in the development of VILI. EGCG may be a potential novel therapeutic candidate for protection against VILI by inhibiting the local release of mtDNA.

[The Clinical Evaluation of Prosthetic Valve in Patients with Dysfunction Valve Endocarditis].

OBJECTIVE: To evaluate the outcomes of valve replacement of endocarditis using bioprothetic and mechanical valves. METHODS: This study comprised 52 patients [mean age (47±18) yr.,mean follow-up time (6.2±3.8) years] underwent valve endocarditis with bioprotheses,The control group were matched (3∶1) with 156 patients of endocarditis underwent mechanical valves replacement using the following variables: age±5 yr.,body mass index (BMI)±20%,time of operation±1 year,replacement position and sex ratio. And evaluate the effects of using bioprothetic and mechanical valves on perioperative and long-term outcomes of valve replacement of endocarditis. RESULTS: The perioperative mortality of the patients receiving bioprothetic and mechanical valves were 17.3%±2.2% and 19.9%±1.8%,respectively,which was independent of valve type (P=0.27). Long-term survival were 56.1%±5.2% and 61.2%±8.1%,respectively (P=0.58). Meanwhile,long-term complication-free survival were 75.0%±3.2% and 82.3%±4.4%,respectively (P=0.29). For the patients younger than or equal to 60 yr.,long-term reoperation rates for bioprothetic and mechanical valves were 41.4%±7.2% and 30.5%±5.4% (P=0.02). For the patients older than 60 yr.,however,reoperation rates were 24.1%±8.5% and 14.7%±5.7% (P=0.36). CONCLUSION: Perioperative mortality and long-term survival are independent to valve types in patients with endocarditis. Mechanical valve shows potential advantage compared with bioprothetic valve in the patients younger than 60-year-old.

[Application of Biological Heart Valves (BHV) and Mechanical Heart Valves (MHV) in the Female Patients of Childbearing Age: a Matched Paired Study].

OBJECTIVE: To observe the efficacy and safety of biological heart valves (BHV) and mechanical heart valves (MHV) in childbearing age women (CAW) during the perinatal and short-moderate term postoperative (SMTP) periods. METHODS: There were 33 patients [(25.2±7.1) yr.] undergoing BHV replacement from September 2009 to December 2014 had completely followed-up,whose data were retrospectively collected. A 1∶4 matching study was conducted,therefore there were 132 patients undergoing MHV were included. The collected date included the clinical outcomes in the perioperative, perinatal,and SMTP period event-free survival (EFS) was determined using the Kaplan-Meier method and compared using the log-rank test. RESULTS: The average follow-up time was (5.8±3.6) years,and the two groups had similar baseline . The clinical outcomes difference of perinatal and SMTP between the two groups were not significant. There were 17 patients in BHV group and 60 in MHV group with pregnancy and birth experiences (PBE),which also showed no significant difference for adverse events both in the maternity and in the fetus. The rates of valve-related adverse events of BHV replacement patients with and without PBE were 5.9% and 0% at 3 years after the operation, and 11.8% and 5.9% after 5 years. PBE was not identified as an adverse prognostic factor for EFS (P=0.43). CONCLUSION: Either artificial BHV or MHV replacement can achieve ideal SMTP effect in CAW. BHV seems not superior to MHV. Pregnancy and birth experience will not increase the risk of BHV relevant adverse events.

Aortoesophageal fistula and arch pseudoaneurysm after removing of a swallowed chicken bone: a case report of one-stage hybrid treatment.

BACKGROUND: Aortoesophageal fistula (AEF) and arch pseudoaneurysm are rare complications induced by a foreign body, and considerable controversy remains regarding the appropriate management strategies. We herein report a successful one-stage hybrid treatment in a patient with AEF and arch pseudoaneurysm. CASE PRESENTATION: The patient, a 40-year-old man, presented to the emergency room because of intense retrosternal discomfort for 3 days and hematemesis for 3 h. The esophagoscopy and thoracic enhanced computed tomography (CT) showed two irregular mural ulcers in the esophagus and a large saccular pseudoaneurysm at the aortic isthmus, respectively. The laboratory examinations confirmed no widespread inflammation and infection. We have successfully performed a successful one-stage hybrid treatment for this patient. Six-month follow-up shows the patient is in good condition and the esophagoscopy reveals the two mural ulcers had completely healed. CONCLUSION: The treatment decision-making process should depend upon the patients' specific situations. Our case suggest the one-stage hybrid treatment could be an valuable alternative in some selected patients.

[The Role of Bone Morphogenic Protein-4 in the Progression of Vein Graft Hyperplastic Remodeling under Hyperglycemic Condition].

OBJECTIVE: This study was designed to assess the vessel wall characteristics and the expression levels of bone morphogenic protein4(BMP4) and proliferating cell antigen Ki67 in vein grafts harvested from diabetic rats,and to investigate the role of BMP4 in progression of vein graft hyperplastic remodeling under hyperglycemic condition. METHODS: 48 male SpragueDawky rats [body mass (194±16) g] aged 8 weeks were randomly divided into diabetes mellitus (DM) group ( n=24) and nondiabetes mellitus (NDM) group ( n=24). The DM rats were induced by streptozotocin in combination with highsugar and highfat diet. The unilateral external jugular vein was interposition grafted into the common carotid arteries in the two groups. The vein grafts were harvested at preoperatively and 1,2 and 4 weeks postoperatively ( n=6) in each group. The morphological characteristics of the venous graft wall were evaluated by hematoxylineosin staining,and the expression levels and the distribution of Ki67 and BMP4 were assessed by immunohistochemistry analysis,then the expression of BMP4 gene and protein was measured by realtime polymerase chain reaction (RTPCR) and Western blot assay respectively. RESULTS: In the progression of rats vein grafts hyperplastic remodeling,the venous wall thickness of rats thickened with time increasing,and the intimal and medial thickness of the vein grafts harvested from DM rats were significantly higher than those from NDM rats at the same time postoperatively ( P<0.05). Ki-67 was highly xpressed in smooth muscle cells nucleus located in the rats vein grafts,and its expression level was up-regulated gradually in the progression of vein graft failure,and the Ki 67 positive cells of vein grafts from DM rats were significantly higher than those from NDM controls at the same period ( P<0.05). Immunohistochemistry analysis showed that BMP4 was expressed in smooth muscle cells cytoplasmof the rats vein grafts,combined with the results of RT-PCR and Western blot assay,there was a little BMP4 expression could be seen in venous wall of NDM rats,while BMP4 positive cells and the expression level of BMP4 gene and protein from DM rats vein grafts was increasing with obvious time dependence and significantly higher than the NDM rats ( P<0.05). CONCLUSION: The morphological and pathological changes within the venous wall were significantly correlated with the high expression levels of BMP4 in vein grafts harvested from diabetic rats,implying a potential role of BMP4 in the progression of accelerated vein graft failure under hyperglycemic condition.

Mitochondrial DNA­induced inflammatory damage contributes to myocardial ischemia reperfusion injury in rats: Cardioprotective role of epigallocatechin.

Inflammation serves an important role in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. Fragments of endogenous damaged­associated molecular patterns, recently identified as mitochondrial DNA (mtDNA), have been proven to be a potent pro­inflammatory mediator. Epigallocatechin­3­gallate (EGCG) is able to regulate the expression levels of a series of inflammatory cytokines. However, the involvement of endogenous mtDNA in EGCG­regulated inflammatory activities in the context of myocardial I/R injury remains to be elucidated. The present study was designed to investigate the role of mtDNA in EGCG­mediated myocardial protection in a rat I/R model. Significant positive correlations between elevated plasma mtDNA copy numbers and the expression levels of tumor necrosis factor (TNF) and interleukins (IL)­6 and ­8 were observed in the myocardial tissue following an I/R injury (P<0.05). However, EGCG administered prior to reperfusion was able to effectively downregulate the expression levels of plasma mtDNA, TNF and IL­6 and ­8 in the myocardial tissue following an I/R injury (P<0.05). Limited infarct size, reduced severity of myocardial injury and decreased incidence of ventricular arrhythmia were observed in the EGCG­treated group. However, the beneficial effects of EGCG in preventing myocardial I/R injury may be eliminated by a specific phosphoinositide­3­kinase (PI3K) inhibitor. These results suggested that EGCG­mediated cardioprotective effects may be achieved by inhibiting the release of mtDNA from damaged mitochondria and that this protection was at least in part dependent on the PI3K/RAC­α serine/threonine­protein kinase associated signaling pathway.

[Epigallocatechin-3-gallate Attenuates Myocardial Reperfusion Injury in Rats Through Activation of PI3K/Akt Signaling Pathway].

OBJECTIVE: This study was designed to investigate whether epigallocatechin-3-gallate (EGCG) postconditioning protects the heart against ischemic-reperfusion injury (IRI), and to explore its potential mechanisms in a rat model. METHODS: Male Wistar rats were subjected to myocardial ischemia (30 min) and reperfusion (up to 2 h) and the rats were divided into sham group (SO) group, ischemia-reperfusion (I/R) model group and EGCG group. EGCG group were treated with EGCG (10 mg/kg) via intravenous infusion 5 min before reperfusion. Electrocardiogram were applied to record ventricular arrhythmia frequency. The severity of myocardial injury [serum level of lactate dehydrogenase (LDH) and creatine kinase (CK), hematoxylineosin (HE) staining] and ventricular arrhythmia, and the serum levels of inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukins-6 (IL-6) and IL-8] were assessed with ELISA, electrocardiogram and Western blot respectively. RESULTS: EGCG given before reperfusion could effectively reduce the serum level of LDH and CK and the incidence of ventricular arrhythmia (P < 0.05, respectively), improved the pathological damage. Meanwhile, EGCG could down-regulate the expression levels of TNF-α, IL-6, IL-8 in the myocardial tissue after IRI (P < 0.05, repectively). The expression levels of p-p85 and p-Akt in the EGCG group were significantly up-regulated compared to those in I/R group (P < 0.05, repectively). CONCLUSION: EGCG-related anti-inflammatory action could attenuate rat myocardial IRI and this cardioprotective effect might be activated through the PI3K/Akt pathway.

[The Association Between Bone Morphogenic Protein-4 and in-situ Saphenous Vein Graft Pathology in Diabetic Patients Undergoing Coronary Revascularization].

OBJECTIVES: This study was designed to assess the expression levels of bone morphogenic protein-4 (BMP4) in saphenous veins harvested from diabetic patients undergoing coronary artery bypass grafting (CABG), and to investigate its association with in-situ morphological and pathological changes within the venous wall. METHODS: From January 2013 to December 2014, forty patients with type 2 diabetes mellitus (DM) and risk factors matched non-DM controls (n =40) were enrolled prospectively. Of the 40 DM patients, 24 had noninsulin-dependent diabetes (NIDM) and the remaining 16 had insulin-dependent diabetes (IDM). Segments of saphenous vein without surgical dilatation from these 80 patients were obtained. Vessel wall characteristics were evaluated by hematoxylin-eosin (HE) staining, and the expression and distribution of BMP4 was assessed by Western blot assay and immunohistochemistry analysis. RESULTS: The intimal and medial thickness of the saphenous veins harvested from DM patients were higher than those from non-DM controls. Compared with non-DM patients, the expression level of BMP4 was significantly elevated in diabetic veins ( P<0.05), and BMP4 was highly expressed in smooth muscle cells located in the medial layer. Moreover, the expression levels of BMP4 in diabetic veins were significantly correlated with intimal thickness (r =0.655, P<0.01), intimal area (r =0.684, P<0.01), medial thickness (r =0.642, P<0.01) and medial area (r =0.692, P<0.01). CONCLUSIONS: The pre-existing intimal and medial hyperplasia were significantly correlated with the high expression levels of BMP4 in saphenous veins harvested from diabetic patients, implying a potential role of BMP4 in the progression of vein graft stenotic diseases in this cohort of post-CABG patients. Future studies were warranted in investigating novel therapeutic strategy targeting at BMP4 for improving long-term vein graft patency.