Optimization of lung ultrasound in ultrafast-track anesthesia for non-cyanotic congenital heart disease surgery.

Objective: We aimed to explore the feasibility of lung ultrasound for perioperative assessment and the optimal effect of lung ultrasound in reducing lung complications during non-cyanotic congenital heart disease (CHD) surgery using ultrafast-track anesthesia. Methods: Sixty patients were treated at Shenzhen Children's Hospital between 2019 and 2020. Of these, 30 patients in group N had an indication for extubation and ultrafast-track anesthesia after congenital heart surgery; the tracheal catheter was removed, and the patients were sent to the cardiac intensive care unit (CICU) for further monitoring and treatment. Another 30 patients were in group L and also had an indication for extubation and ultrafast-track anesthesia; in addition we compared lung ultrasound score (LUS) before and after surgery, when we found the cases that LUS ≥ 15, for whom targeted optimization treatment would be carried out. The tracheal catheter was removed after LUS <15 days before the patients were sent to the CICU. In all cases, the LUS and PaO2/FiO2 ratios (P/F) of both groups were recorded at the time of anesthesia induction (T0), before extubation (T1), and 5 min (T2), 1 h (T3), and 24 h (T4) after extubation. The incidence of pulmonary complications, LUS, and P/F were compared between the two groups. Results: There was great consistency between LUS and radiographic findings. Comparing the data of the two groups at T2, T3 and T4, the P/F was higher and the LUS was lower in group L than in group N. The incidence of lung complications in group L (18 cases, 60 %) was lower than that in group N (26 cases, 86.7 %, χ2 = 5.46, P = 0.02); comparing LUS between T0 and T3, LUS decreased in a greater number of cases in group L (15, 50 %) than in group N (7 cases, 23.3 %, χ2 = 4.59, P = 0.032). Conclusion: Lung ultrasonography can effectively help assess lung conditions. Optimization guided by lung ultrasound in ultrafast track anesthesia can significantly reduce postoperative lung complications.

Endomyocardial fibrosis and apical calcification: A case report with unusual presentations of apical hypertrophic cardiomyopathy.

RATIONALE: Apical hypertrophic cardiomyopathy (ApHCM) is a phenotypic variant of hypertrophic cardiomyopathy. Endomyocardial fibrosis and endocardial calcification are especially rare in ApHCM. PATIENT CONCERNS: The main symptoms was chest tightness, palpitation, shortness of breath, and fatigue. Echocardiography and imaging examinations found apical hypertrophy along with endocardial calcification and endomyocardial fibrosis. Abnormal structural changes led to thrombosis and made the left ventricle a flat shape resembling an "apple." DIAGNOSES: The typical presentations, hypertrophic apex on echocardiography and an elevated N-terminal pro-brain natriuretic peptide level indicated the diagnosis of ApHCM and heart failure with preserved ejection fraction. INTERVENTIONS: Optimal medical therapy including the administration of ApHCM, heart failure and atrial fibrillation to improve symptoms and life quality. OUTCOMES: Since discharge, the patient could perform normal daily activities and had no discomfort based on the optimal medical therapy. LESSONS: We report a ApHCM patients with unusual presentations of endomyocardial fibrosis and apical calcification. This case highlights the importance of understanding the specific pathological changes of ApHCM for treatment and prognosis.

Cardiac contractility modulation ameliorates myocardial metabolic remodeling in a rabbit model of chronic heart failure through activation of AMPK and PPAR-α pathway.

Metabolic remodeling contributes to the pathological process of heart failure (HF). We explored the effects of cardiac contractility modulation (CCM) on myocardial metabolic remodeling in the rabbit model with HF. The HF in rabbit model was established by pressure uploading and then CCM was applied. We evaluated the cardiac structure and function by echocardiography, serum BNP level, and hematoxylin and eosin and Masson's trichrome staining. We detected the accumulation of glycogen and lipid droplets in myocardial tissues by periodic acid-Schiff and Oil Red O staining. Then, we measured the contents of glucose, free fatty acid (FFA), lactic acid, pyruvate, and adenosine triphosphate (ATP) levels in myocardial tissues by corresponding kits and the expression levels of key factors related to myocardial substrate uptake and utilization by western blotting were analyzed. CCM significantly restored the cardiac structure and function in the rabbit model with HF. CCM therapy further decreased the accumulation of glycogen and lipid droplets. Furthermore, CCM reduced the contents of FFA, glucose, and lactic acid, and increased pyruvate and ATP levels in HF tissues. The protein expression levels related to myocardial substrate uptake and utilization were markedly improved with CCM treatment by further activating adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptor-α signaling pathways.

Clinical Significance of MiR-27a Expression in Serum Exosomes in Patients with Heart Failure.

To study the clinical significance of miR-27a expression in serum exosomes in patients with heart failure (HF), this study was carried out. Totally 101 chronic heart failure (CHF) patients (research group) admitted to our hospital from April 2016 to January 2019 were enrolled, and another 30 healthy subjects (control group) who underwent physical examination during the same period were selected. The difference of miR-27a expression level in serum exosomes between the two groups of subjects was compared, so as to analyze the diagnostic value of miR-27a in CHF and the relationship between miR-27a expression level and patient prognosis. The expression level of miR-27a in peripheral blood exosomes of subjects in the control group (CG) was significantly higher than that in the research group (RG) (P<0.05), while the miR-27a expression of the latter increased significantly 3 months after treatment (P<0.05). ROC analysis showed that the AUC, sensitivity, specificity, and critical level of miR-27a in the diagnosis of CHF were 0.835, 77.23%, 80.00%, and 1.060 respectively. While after 3 months of treatment, the indicators of the RG effectively improved (P<0.05). Pearson and Sparman correlation analysis revealed that there was a significant linear correlation between miR-27a and each indicator (P<0.05). K-M survival curve analysis demonstrated that the survival rate of patients with high expression of miR-27a was significantly higher than that of patients with low expression (P<0.05). The expression of mR-27a in serum exosomes is decreased in patients with HF and has important potential value in the diagnosis and prognosis of CHF.

The Expression of miR-365 in Serum of Hypertension Patients with Left Ventricular Hypertrophy Was Up-Regulated, Which Was Positively Correlated with Left Ventricular Mass Index.

OBJECTIVE: The present study aims to investigate micro ribonucleic acid-365 (miR-365) serum expression and its correlation with left ventricular hypertrophy (LVH) in patients with hypertension (HT). METHODS: Eighty-four patients were selected as study subjects and divided into three groups: the experimental group (n = 28), the observation group (n = 29), and the control group (n = 27). The experimental group included patients with LVH-accompanied HT who were treated in the People's Hospital of Hebei Province between November 2019 and November 2020, the observation group included patients with HT unaccompanied by LVH, and the control group included healthy age and gender-matched subjects who underwent health examinations in our physical examination center. The cardiac echocardiography, 24-h Holter electrocardiogram, and circulating miR-365 levels in all subjects were measured. The differences in circulating miR-365 expression levels among the three groups were compared, and the correlations between the miR-365 expression levels and the blood pressure parameters (24-h mean systolic blood pressure [SBP] and 24-h mean diastolic blood pressure [DBP]), inter-ventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular internal diameter (LVID), left ventricular mass (LVM), LVM index (LVMI), and LVH-related indicators were analyzed. RESULTS: The relative miR-365 expressions in the experimental, observation, and control groups were 2.08 (1.60, 2.34), 0.62 (0.44, 0.83), and 0.66 (0.35, 0.86), respectively. Patient miR-365 expression was significantly higher in the experimental group than in the observation group and the control group; the differences were statistically significant (p < 0.000). Furthermore, miR-365 expression was significantly correlated with SBP, DBP, IVST, LVPWT, LVID, LVM, and LVMI; the greatest correlation was with LVMI. Further univariate linear regression analysis revealed that miR-365 expression was linearly and positively correlated with LVMI and that miRNA-365 expression increased with the LVMI value. CONCLUSION: The miR-365 serum expression in patients with LVH-accompanied HT was increased compared with the observation group and the control group and positively correlated with the LVH degree.

Thrombus aspiration during primary percutaneous coronary intervention improved outcome in patients with STEMI and a large thrombus burden.

BACKGROUND: The benefit of thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) to patients with ST-segment elevation myocardial infarction (STEMI) remains controversial. This study aimed to assess TA's impact on the outcome and prognosis for patients with STEMI and a large thrombus burden during PPCI. METHODS: This retrospective study evaluated consecutive patients with STEMI and a large thrombus burden (thrombolysis in myocardial infraction [TIMI] thrombus grade ≥4) who underwent conventional PPCI (n = 126) or PPCI + TA (n = 208) between February 2017 and January 2019. The procedure outcome and clinical prognosis were compared. RESULTS: Postprocedural vessel diameter was larger, and corrected TIMI frame count (cTFC) was lower in the PPCI + TA compared with the PPCI group. The proportion of postprocedural TIMI 3 flow was 83.3% in the PPC group and 94.2% in the PPCI+TA group. During the 12-month follow-up, no significant differences existed in the incidence of cardiac death, reinfarction, stent thrombosis, target vessel revascularization, or stroke. CONCLUSION: Application of TA in patients with STEMI and a large thrombus burden during PPCI may improve the procedural outcome, but it showed no benefit on the clinical prognosis in the 12-month follow-up. Longer follow-up studies are needed to confirm TA's clinical implications in patients with STEMI.

miR-362-3p Targets Orosomucoid 1 to Promote Cell Proliferation, Restrain Cell Apoptosis and Thereby Mitigate Hypoxia/Reoxygenation-Induced Cardiomyocytes Injury.

This study aimed to investigate the mechanism of how miR-362-3p/orosomucoid 1 (ORM1) involved in hypoxia/reoxygenation (H/R)-induced cardiomyocytes injury. Based on data obtained from Gene Expression Omnibus (GEO) database, we revealed that ORM1 was highly expressed and positively correlated with the expression of inflammatory factors (MAPK1, MAPK3, IL1B and CASP9). miR-362-3p was identified as an upstream regulatory miRNA of ORM1 and negatively modulated the mRNA and protein expression levels of ORM1 in H/R-injured cardiomyocytes. Moreover, we found that miR-362-3p was downregulated in cardiomyocytes injured by H/R. The promoting influence of miR-362-3p mimic on the proliferation and the inhibitory effect of miR-362-3p mimic on the apoptosis of H/R-stimulated cardiomyocytes were eliminated by overexpression of ORM1. Furthermore, miR-362-3p affected the expression of MAPK1, MAPK3, IL1B and CASP9 in H/R-injured cardiomyocytes through targeting ORM1. Our outcomes illustrated that miR-362-3p exhibited a protective influence on H/R-induced cardiomyocytes through targeting ORM1.

Total Glucosides of Paeony Alleviate Cell Apoptosis and Inflammation by Targeting the Long Noncoding RNA XIST/MicroRNA-124-3p/ITGB1 Axis in Renal Ischemia/Reperfusion Injury.

OBJECTIVE: Renal ischemia/reperfusion injury (RI/RI) is the main cause of acute kidney injury. Total glucosides of paeony (TGP) are a traditional Chinese medicine. This study was aimed at exploring the role of TGP in RI/RI and its underlying mechanism of action. METHODS: Rat RI/RI models were constructed by surgical operation. Serum creatinine (Scr) and blood urea nitrogen (BUN) were used to evaluate renal function. The levels of proinflammatory cytokines were detected by ELISA. RI/RI was simulated by hypoxia/reoxygenation (H/R) treatment in renal cells in vitro. The lncRNA XIST (XIST) expression was analyzed by qRT-PCR. Then, the viability and apoptosis of renal cells were detected by MTT and flow cytometry assay. Additionally, dual-luciferase reporter assay was used to determine the interactions among XIST, microRNA-124-3p (miR-124-3p), and ITGB1. RESULTS: TGP improved renal function and inhibited inflammatory responses after RI/RI. XIST expression was highly expressed in rat RI/RI models and H/R-treated renal cells, whereas treatment with TGP downregulated the XIST expression. Additionally, TGP increased viability and attenuated apoptosis and inflammation of H/R-treated renal cells via inhibiting XIST. Moreover, XIST was competitively bound to miR-124-3p, and ITGB1 was a target of miR-124-3p. miR-124-3p overexpression or ITGB1 inhibition rescued the reduction effect on viability and mitigated the promoting effects on cell apoptosis and inflammation caused by XIST overexpression in H/R-treated renal cells. CONCLUSIONS: In vivo, TGP attenuated renal dysfunction and inflammation in RI/RI rats. In vitro, TGP inhibited XIST expression to modulate the miR-124-3p/ITGB1 axis, alleviating the apoptosis and inflammation of H/R-treated renal cells.

Combination of serum TIMP-3, CA125, and NT-proBNP in predicting ventricular remodeling in patients with heart failure following acute myocardial infarction.

BACKGROUND: Left ventricular remodeling is the basic pathological mechanism of heart failure following acute myocardial infarction (AMI). Determining sensitive indexes for the early prediction of ventricular remodeling is important for the prevention of heart failure. This study aims to investigate the value of serum TIMP-3, CA125, and NT-proBNP in predicting ventricular remodeling in patients with heart failure following AMI. METHODS: From May 2017 to May 2018, 93 patients with heart failure following AMI were enrolled in the study. The participants were divided into two groups: the ventricular remodeling group (n=51) and the non-ventricular remodeling group (n=42). In addition, 47 healthy subjects who underwent physical examinations in the same period were enrolled as controls. Serum TIMP-3, CA125, and NT-proBNP were measured, in addition to the left ventricular wall thickness (LVWT) and left ventricular mass index (LVMI). The correlation of serum TIMP-3, CA125, and NT-proBNP with the LVWT and LVMI was analyzed, and its value in predicting ventricular remodeling was evaluated. RESULTS: Serum TIMP-3 level was lower (P<0.05) and CA125 and NT-proBNP levels were higher (P<0.05) in both the ventricular remodeling and non-ventricular remodeling groups compared with the control group. Furthermore, the serum TIMP-3 level was lower in the ventricular remodeling group compared with the non-ventricular remodeling group (P<0.05), while the levels of CA125 and NT-proBNP were higher in the ventricular remodeling group compared with the non-ventricular remodeling group (P<0.05). The serum TIMP-3 level was negatively correlated with the LVWT and LVMI, while serum CA125 and NT-proBNP levels were positively correlated with the LVWT and LVMI, respectively. The area under the receiver operating characteristic curve of the combination of serum TIMP-3, CA125, and NT-proBNP levels in predicting ventricular remodeling was 0.850, and the prediction sensitivity and specificity were 74.51% and 87.71%, respectively. CONCLUSIONS: The combination of serum TIMP-3, CA125, and NT-proBNP can improve the sensitivity and specificity of predicting ventricular remodeling and can aid in the early prevention and treatment of heart failure.

CAR T-cell therapy for triple-negative breast cancer: Where we are.

Triple-negative breast cancer (TNBC) is the most complex and challenging breast cancer subtype to treat, and chemotherapy remains the standard of care. Clinically, TNBC has a relatively high rate of recurrence and poor prognosis, which leads to a significant effort to discover novel strategies to treat patients with these tumors. Currently, chimeric antigen receptor (CAR) T cell-based immunotherapy redirects the patient's immune system directly to recognize and eradicate tumor-associated antigens (TAAs) expressing tumor cells being explored as a treatment for TNBC. A steadily increasing research in CAR T-cell therapy targeting different TAAs in TNBC has reported. In this review, we introduce the CAR technology and summarize the potential TAAs, available CARs, the antitumor activity, and the related toxicity of CARs currently under investigation for TNBC. We also highlight the potential strategies to prevent/reduce potential "on target, off tumor" toxicity induced by CAR T-cell therapy. This review will help to explore proper targets to expand further the CAR T-cell therapy for TNBCs in the clinic.

Research progress of CA125 and BDNF in serum of patients with acute myocardial infarction for predicting acute heart failure.

BACKGROUND: At present, the treatment for acute myocardial infarction has achieved great progress. Reperfusion therapy in the short term can effectively reduce recurrence rates and mortality in patients with acute myocardial infarction. According to a report of a large national registry, the mortality of patients with acute coronary syndrome combined with acute heart failure is 10 times of that of patients without heart failure, and the mortality in nearly 10 years has no significant change. Therefore, people are constantly exploring indicators for acute heart failure prognosis to improve a patient's prognosis. With the constant understanding and exploration of acute myocardial infarction, more and more researches have focused in determining how to predict the occurrence of acute heart failure. The present study focuses on presenting the latest progress of Carbohydrate Antigen-125 (CA125) and Brain Derived Neurotrophic Factor (BDNF) in serum of patients with acute myocardial infarction in predicting acute heart failure.

Optical coherence tomography guided successful treatment without stent implantation in a patient with non-ST-segment elevation myocardial infarction caused by plaque rapture: A case report.

RATIONALE: Primary percutaneous coronary intervention (PPCI) with immediate stenting provides effective revascularization. While the risks of no-reflow, stent thrombosis, stent undersizing, and malapposition reduced the benefits in patients with high burden thrombosis. Intravascular imaging, especially optical coherence tomography (OCT), offers potential in optimization of percutaneous coronary intervention. PATIENT CONCERNS: A 51-year-old male underwent coronary angiography (CAG) due to chest pain with minimal ST-segment depression of the electrocardiogram. DIAGNOSES: Urgent CAG revealed burden thrombus in the mid left anterior descending coronary artery (LAD) with TIMI grade I distal flow. INTERVENTIONS: After aspiration thrombectomy, OCT was used to evaluate the target lesion of non-ST-segment elevation myocardial infarction (NSTEMI) and conservative treatment without stent implantation was selected. OUTCOMES: CAG repeated 1 month after PPCI revealed TIMI grade III blood flow in LAD and only minimal stenosis in the target lesion. OCT showed a cavity formation due to plaque rupture and MLA increased after thrombus dissolution. Follow-up was uneventful at 6 months. LESSONS: OCT may be useful imaging modality to identify the characteristic of culprit lesion of acute myocardial infarction and subsequently guide individual treatment.

Inhibition of SETD7 protects cardiomyocytes against hypoxia/reoxygenation-induced injury through regulating Keap1/Nrf2 signaling.

The protein SET domain-containing lysine methyltransferase 7 (SETD7) has recently been shown to regulate apoptosis in various cells. However, the role of SETD7 on cardiomyocyte apoptosis during myocardial ischemia/reperfusion injury remains unclear. This study aimed to investigate the potential role of SETD7 in hypoxia/reoxygenation (H/R)-induced apoptosis of rat cardiomyocytes and reveal the underlying mechanism. Our results demonstrated that SETD7 expression was significantly up-regulated in cardiomyocytes in response to H/R injury. The inhibition of SETD7 by siRNA-mediated gene silencing significantly suppressed H/R-induced apoptosis and decreased the production of reactive oxygen species (ROS). The overexpression of SETD7 markedly enhanced H/R-induced apoptosis and ROS production. Moreover, the knockdown of SETD7 reduced the expression of Keap1 and promoted the expression of Nrf2. In addition, the knockdown of SETD7 increased the activity of antioxidant response element and promoted the expression of heme oxygenase-1 and NADPH-quinone oxidoreductase 1. However, the knockdown of Nrf2 partially abrogated the SETD7 inhibition-mediated protective effect against H/R injury. Taken together, these results indicate that the inhibition of SETD7 attenuates H/R-induced injury of cardiomyocytes via the down-regulation of Keap1 and promotion of the Nrf2-mediated anti-oxidation signaling pathway.