Association of Preablation Plasma Corin Levels With Atrial Fibrillation Recurrence After Catheter Ablation: A Prospective Observational Study.

BACKGROUND: We assessed the impact of pre- and postprocedural plasma corin levels on the recurrence of atrial fibrillation (AF) after catheter ablation (CA). METHODS AND RESULTS: This prospective, single-center, observational study included patients undergoing their first CA of AF. Corin was measured before and 1 day after CA. The primary end point was recurrent AF between 3 and 12 months after ablation. From April 2019 through May 2021, we analyzed 616 patients with AF (59.09% men) with a mean age of 62.86±9.42 years. Overall, 153 patients (24.84%) experienced recurrent AF. In the recurrence group, the pre- and postprocedure corin concentrations were 539.14 (329.24-702.08) and 607.37 (364.50-753.80) pg/mL, respectively, which were significantly higher than the nonrecurrence group's respective concentrations of 369.05 (186.36-489.28) and 489.12 (315.66-629.05) pg/mL (both P<0.0001). A multivariate Cox regression analysis with confounders found that elevated preablation corin levels were significantly associated with an increased risk of AF recurrence after CA. Receiver operating characteristic curve analysis identified that a preablation corin threshold of >494.85 pg/mL predicted AF recurrence at 1 year. An increase of 1 SD in corin concentrations before CA (264.94 pg/mL) increased the risk of recurrent AF by 54.3% after adjusting for confounding variables (hazard ratio, 1.465 [95% CI, 1.282-1.655]; P<0.0001). CONCLUSIONS: Plasma corin levels at baseline is a valuable predictor of AF recurrence after CA, independent of established conventional risk factors. Risk stratification before ablation for AF may be useful in selecting treatment regimens for patients.

Total Syntheses of Brassicicenes A, R, and T.

Here, we report concise and divergent total syntheses of fusicoccane members brassicicenes A, R, and T. The key feature of the synthesis is the rapid construction of the 5/8/5 tricyclic core via four steps: aldol reaction, Stork-Danheiser transposition, and ring-closing metathesis from known compounds followed by concise oxidation state adjustment.

Benefit of Catheter Ablation for Atrial Fibrillation in Heart Failure Patients with Different Etiologies.

(1) Background: A plethora of studies have elucidated the safety and efficacy of catheter ablation (CA) for patients afflicted with atrial fibrillation (AF) and concomitant reduction in left ventricular ejection fraction (LVEF). Nevertheless, the literature on the benefits of CA in the specific etiological context of heart failure (HF) remains limited. This study delineates a comparative assessment of outcomes for patients with AF and reduced LVEF across the primary etiologies. (2) Methods: Our inquiry encompassed 216 patients diagnosed with congestive heart failure and an LVEF of less than 50 percent who were referred to our institution for circumferential pulmonary vein isolation (CPVI) between the years 2016 and 2020. The selection criteria included a detailed medical history while excluding those suffering from valvular disease, congenital heart disease, and hypertrophic cardiomyopathy. In an effort to scrutinize varying etiologies, patients were stratified into three categories: dilated cardiomyopathy (DCM, n = 56, 30.6%), ischemic cardiomyopathy (ICM, n = 68, 37.2%), and tachycardia-induced cardiomyopathy (TIC, n = 59, 32.2%). (3) Results: Following an average (±SD) duration of 36 ± 3 months, the prevalence of sinus rhythm was 52.1% in the DCM group, 50.0% in the ICM group, and 68.14% in the TIC group (p = 0.014). This study revealed a significant disparity between the DCM and TIC groups (p = 0.021) and the ICM and TIC groups (p = 0.007), yet no significant distinction was discerned between the TIC and ICM groups (p = 0.769). Importantly, there were no significant variations in the application of antiarrhythmic drugs or recurrence of procedures among the three groups. The mortality rates were 14.29% for the DCM group and 14.71% for the ICM group, which were higher than the 3.39% observed in the TIC group (DCM vs. TIC p = 0.035 (HR = 4.50 (95%CI 1.38-14.67)), ICM vs. TIC p = 0.021 (HR = 5.00 (95%CI 1.61-15.50))). A noteworthy enhancement in heart function was evidenced in the TIC group in comparison to the DCM and ICM groups, including a higher LVEF (p < 0.001), diminution of LV end-diastolic diameter (p < 0.001), and an enhanced New York Heart Association classification (p = 0.005). Hospitalization rates for heart failure were discernibly lower in TIC patients (0.98 (0,2) times) relative to those with DCM (1.74 (0,3) times, p < 0.01) and TIC (1.78 (0,4) times, p < 0.001). Patients with paroxysmal atrial fibrillation and brief episodes were found to achieve superior clinical outcomes through a catheter ablation strategy. (4) Conclusion: Patients diagnosed with TIC demonstrated a more pronounced benefit from catheter ablation compared to those with DCM and ICM. This encompassed an augmented improvement in cardiac function, an enhanced maintenance of sinus rhythm, and a reduced mortality rate.

Dual hypoxia-responsive supramolecular complex for cancer target therapy.

The prognosis with pancreatic cancer is among the poorest of any human cancer. One of the important factors is the tumor hypoxia. Targeting tumor hypoxia is considered a desirable therapeutic option. However, it has not been translated into clinical success in the treatment of pancreatic cancer. With enhanced cytotoxicities against hypoxic pancreatic cancer cells, BE-43547A2 (BE) may serve as a promising template for hypoxia target strategy. Here, based on rational modification, a BE prodrug (NMP-BE) is encapsulated into sulfonated azocalix[5]arene (SAC5A) to generate a supramolecular dual hypoxia-responsive complex NMP-BE@SAC5A. Benefited from the selective load release within cancer cells, NMP-BE@SAC5A markedly suppresses tumor growth at low dose in pancreatic cancer cells xenograft murine model without developing systemic toxicity. This research presents a strategy for the modification of covalent compounds to achieve efficient delivery within tumors, a horizon for the realization of safe and reinforced hypoxia target therapy using a simple approach.

Effect of Mo Oxides on the Phase Composition and Characteristics of Mo-10Re Pre-Alloyed Powders Co-Reduced with NH4ReO4.

Mo-Re pre-alloyed powders are crucial raw materials in fabricating Mo-Re alloys, and their properties can significantly impact the properties of the resulting alloys. The powders are usually produced by the co-reduction of a mixture of Mo and Re oxides. However, it remains unclear if the overall characteristics of the produced Mo-Re powders rely on the different combinations of the Mo and Re oxide precursors. Therefore, in this work, a comparative study is conducted on the co-reduction processes of different Mo oxides together with NH4ReO4, along with its influence on the size distribution and phase composition of the resulting Mo-10Re pre-alloyed powders. The results show that MoO3 is more promising than MoO2 as a precursor material. The powders fabricated using MoO3, when compared to MoO2, have a much more uniform size distribution, with a primary particle size ranging from 0.5-4 µm. In addition, it is also beneficial to achieve atomic-scale homogeneous mixing with Mo and Re elements and the formation of a solely Mo(Re) solid solution if MoO3 is used as a precursor oxide. In contrast, such desirable features were not identified when using the MoO2 route. The reason for this discrepancy may relate to whether Mo-O-Re metallurgical bonding has formed during the co-reduction process.

Catheter ablation of atrial fibrillation using FireMagic TrueForce ablation catheter: The TRUEFORCE trial.

BACKGROUND: The use of contact force (CF) sensing catheters has provided a revolutionary improvement in catheter ablation (CA) of atrial fibrillation (AF) in the past decade. However, the success rate of CA for AF remains limited, and some complications still occur. METHODS: The TRUEFORCE trial (Catheter Ablation of Atrial Fibrillation using FireMagic TrueForce Ablation Catheter) is a multicenter, prospective, single-arm objective performance criteria study of AF patients who underwent their first CA procedure using FireMagic TrueForce ablation catheter. RESULTS: A total of 120 patients (118 with paroxysmal AF) were included in this study, and 112 patients included in the per-protocol analysis. Pulmonary vein isolation (PVI) was achieved in 100% of the patients, with procedure and fluoroscopy time of 146.63 ± 40.51 min and 12.89 ± 5.59 min, respectively. Freedom from recurrent atrial arrhythmia after ablation was present 81.25% (95% confidence interval [CI]: 72.78%-88.00%) of patients. No severe adverse events (death, stroke/transient ischemic attack [TIA], esophageal fistula, myocardial infarction, thromboembolism, or pulmonary vein stenosis) were detected during the follow-up. Four (4/115, 3.33%) adverse events were documented, including one abdominal discomfort, one femoral artery hematoma, one coughing up blood, and one postoperative palpitation and insomnia. CONCLUSIONS: This study demonstrated the clinical feasibility of FireMagic force-sensing ablation catheter in CA of AF, with a satisfactory short- and long-term efficacy and safety.

Discovery of orally effective and safe GPR40 agonists by incorporating a chiral, rigid and polar sulfoxide into ß-position to the carboxylic acid.

GPR40 is primarily expressed in pancreatic islet ß-cells, and its activation by endogenous ligands of medium to long-chain free fatty acids or synthetic agonists is clinically proved to improve glycemic control by stimulating glucose-dependent insulin secretion. However, most of the reported agonists are highly lipophilic, which might cause lipotoxicity and the off-target effects in CNS. Particularly, the withdrawal of TAK-875 from clinical trials phase III due to liver toxicity concern threw doubt over the long-term safety of targeting GPR40. Improving the efficacy and the selectivity, thus enlarging the therapeutic window would provide an alternative to develop safe GPR40-targeted therapeutics. Herein, by employing an innovative "three-in-one" pharmacophore drug design strategy, the optimal structural features for GPR40 agonist was integrated into one functional group of sulfoxide, which was incorporated into the ß-position of the propanoic acid core pharmacophore. As a result, the conformational constraint, polarity as well as chirality endowed by the sulfoxide significantly enhanced the efficacy, selectivity and ADMET properties of the novel (S)- 2-(phenylsulfinyl)acetic acid-based GPR40 agonists. The lead compounds (S)-4a and (S)-4s exhibited robust plasma glucose-lowering effects and insulinotropic action during an oral glucose tolerance test in C57/BL6 mice, excellent pharmacokinetic profile and little hepatobiliary transporter inhibition, marginal cell toxicities against human primary hepatocyte at 100 µM.

Convergent synthesis of tetrahydropyranyl side chain of verucopeptin, an antitumor antibiotic active against multidrug-resistant cancers.

A concise synthesis of the tetrahydropyranyl side chain of verucopeptin, an antitumor antibiotic cyclodepsipeptide efficacious against MDR cancers in vivo, is achieved using 12 steps in the longest linear sequence and 21 total steps, in which Julia-Kocienski olefination for the segments coupling, asymmetric hydroxylation as well as stereoselective synthesis of stable tetrahydropyran ring from a D-isoascorbic acid derivative are key steps. This convergent synthetic strategy enables the structural modification and mechanism study of verucopeptin for its clinical applications.

Cardiomyopathy induced by premature ventricular contractions with ventricular escape beats in the compensatory pause: A case report and brief review of the literature.

RATIONALE: We reported a case with cardiomyopathy induced by frequent premature ventricular contractions (PVCs) and followed ventricular escape beats (VEBs). PVCs with VEBs in the compensatory pause which induced cardiomyopathy is rarely reported. Also, the case exhibited many characteristics of PVCs which were more likely to induce cardiomyopathy, like the location of origin, the longer coupling interval, and the QRS wave companied with the P wave. PATIENT CONCERNS: A 53-year-old man with left ventricular (LV) dysfunction presented with palpation, chest distress, and dyspnea for 3 years. Holter revealed a high burden of ventricular rhythm of PVCs and another wide QRS patterns (96,562 total beats with 87,330 wide QRS beats in 24 hours). The LV ejection fraction decreased to 34% and the left ventricle, right and left atria all dilated. DIAGNOSIS: He was diagnosed with PVC-induced cardiomyopathy. INTERVENTIONS: The patient experienced intracardiac electrophysiological examination which revealed frequent PVCs followed by VEBs in the compensatory pause. Activation mapping of the PVCS and ablation were performed. OUTCOMES: PVCs and VEBs disappeared after ablation. The LV ejection fraction increased to 46% at 2 days after the procedure. The diameters of the right and left atria were also significantly reduced. LESSONS: VEBs may occur during the compensatory pause of PVCs. PVCs with VEBs can lead to a high burden of ventricular rhythm and LV dysfunction. Ablation of the PVCs can also eliminate VEBs and improve the LV function.

Optimal Catheter Ablation Strategy for Patients with Persistent Atrial Fibrillation and Heart Failure: A Retrospective Study.

The optimal catheter ablation (CA) strategy for patients with persistent atrial fibrillation (PeAF) and heart failure (HF) remains uncertain. Between 2016 and 2020, 118 consecutive patients with PeAF and HF who underwent the CA procedure in two centers were retrospectively evaluated and divided into the pulmonary vein isolation (PVI)-only and PVI + additional ablation groups. Transthoracic echocardiography (TTE) was performed at baseline, one month, and 12 months after the CA procedure. The HF symptoms and left ventricular ejection fraction (LVEF) improvements were analyzed. Fifty-six patients underwent PVI only, and 62 patients received PVI with additional ablation. Compared with the baseline, a significant improvement in the LVEF and left atrial diameter postablation was observed in all patients. No significant HF improvement was detected in the PVI + additional ablation group than in the PVI-only group (74.2% vs. 71.4%, P = 0.736), but the procedure and ablation time were significantly longer (137.4 ± 7.5 vs. 123.1 ± 11.5 min, P = 0.001). There was no significant difference in the change in TTE parameters and the number of rehospitalizations. For patients with PeAF and HF, CA appears to improve left ventricular function. Additional ablation does not improve outcomes and has a significantly longer procedure time. Trial registration number is as follows: ChiCTR2100053745 (Chinese Clinical Trial Registry; https://www.chictr.org.cn/index.aspx).

Probe Synthesis Reveals Eukaryotic Translation Elongation Factor†1 Alpha†1 as the Anti-Pancreatic Cancer Target of BE-43547A2.

The natural product, BE-43547A2 , decreases pancreatic cancer cell stemness. However, its anticancer molecular mechanisms have not been fully established. Based on structure-activity relationships of BE-43547A2 , we synthesized a probe and investigated its potential targets using an in situ click reaction. We found that BE-43547A2 exerts its anticancer effects by covalently binding the cysteine234 (C234) residue of eukaryotic translation elongation factor 1 alpha 1 (eEF1A1). This binding mode was confirmed by a series of experiments including a xenograft mouse model. We also determined that eEF1A1 plays an important role in regulating pancreatic cancer cell stemness. Analyses of 99 clinical pancreatic cancer samples revealed that eEF1A1 expressions are closely correlated with clinicopathological grade and patient survival. In conclusion, eEF1A1 is involved in pancreatic cancer progression and is therefore, a promising novel covalent target for pancreatic cancer treatment.

Impact of baseline impedance of pulmonary vein antrum on success of catheter ablation for paroxysmal atrial fibrillation guided by ablation index.

OBJECTIVE: Ablation index (AI) is an effective ablation quality marker. Impedance is also an important factor for lesion formation. The present study evaluated the influence of the baseline impedance in the effect of ablation for atrial fibrillation (AF) guided by AI. METHODS: This was a retrospective study. 101 patients with paroxysmal AF (PAF) were enrolled. All patients underwent radiofrequency ablation guided by the same AI strategy. The ablation strategy was pulmonary vein (PV) isolation with non-PV triggers ablation. The baseline impedance of the ablation points was recorded. The patients were followed up every 3 months or so. RESULTS: During a median follow-up of 12 (4-14) months, freedom from AF/atrial tachycardia recurrence were 82.2%. No difference existed in baseline characteristics between the success group and the recurrence group. The average baseline impedance was 124.3 ± 9.7 Ω. The baseline impedance of the ablation points in success group was lower compared to the recurrence group (122.9 ± 9.4 vs. 130.5 ± 8.8 Ω, P < 0.01). The ratio of impedance drop in the success group was higher than the recurrence group ([8.8 ± 1.4]% vs. [8.1 ± 1.2]%, P = 0.03). Multivariate analysis revealed that baseline impedance, PAF duration and AI were the independent predictors of AF recurrence. The cumulative free of recurrence rate of low-impedance group (≤ 124 Ω, n = 54) was higher than that of high-impedance group. CONCLUSION: Baseline impedance correlates with clinical outcome of radiofrequency ablation for PAF guided by AI. Higher impedance in the same AI strategy may result in an ineffective lesion which probably causes recurrence.

Long Atrial Fibrillation Duration and Early Recurrence Are Reliable Predictors of Late Recurrence After Radiofrequency Catheter Ablation.

Background: Recurrence after atrial fibrillation (AF) ablation is still common. Objective: This study aimed to evaluate the predictive abilities of AF duration and early recurrence (ER) to discriminate high-risk patients for recurrence. Methods: We enrolled 1,763 consecutive patients with AF who were scheduled to receive the index radiofrequency catheter ablation (RFCA) from January 2016 to August 2021 in Dalian, China. Long AF duration (LAFD) was considered if the course of AF lasted for ≥ 12 months. ER was defined as any atrial tachycardia (AT) or AF event longer than 30 s occurring within a 3-month post-RFCA. Results: Late recurrence occurred in 643 (36.5%) of the 1,763 patients at a median of 35 months after RFCA. Multivariate analysis identified LAFD (hazard ratio (HR): 1.80, 95% confidence interval (CI): 1.38-2.35, p < 0.001) and ER (HR: 2.34, 95% CI: 1.82-3.01, p < 0.001) as strong independent predictors of late recurrence in non-paroxysmal AF. Similarly, LAFD (HR: 1.48, 95% CI: 1.20-1.84, p < 0.001) and ER (HR: 3.40, 95% CI: 2.68-4.30, p < 0.001) were significantly associated with late recurrence in paroxysmal AF. Receiver operating curve analyses revealed that the CAAP-AF (CAD, Atrial diameter, Age, Persistent or longstanding AF, Antiarrhythmic drugs failed, Female) had the highest predict power [area under ROC curve (AUC) 0.586]. The addition of ER and LAFD to the CAAP-AF score significantly improved risk discrimination for late recurrence after AF ablation from 0.586 to 0.686. Conclusion: Long AF duration and ER were independently associated with late recurrence. The prediction performance of the CAAP-AF model for recurrence was improved by the addition of LAFD and ER.

Elastase Inhibitor Cyclotheonellazole A: Total Synthesis and In Vivo Biological Evaluation for Acute Lung Injury.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the most common complications in COVID-19. Elastase has been recognized as an important target to prevent ALI/ARDS in the patient of COVID-19. Cyclotheonellazole A (CTL-A) is a natural macrocyclic peptide reported to be a potent elastase inhibitor. Herein, we completed the first total synthesis of CTL-A in 24 linear steps. The key reactions include three-component MAC reactions and two late-stage oxidations. We also provided seven CTL-A analogues and elucidated preliminary structure-activity relationships. The in vivo ALI mouse model further suggested that CTL-A alleviated acute lung injury with reductions in lung edema and pathological deterioration, which is better than sivelestat, one approved elastase inhibitor. The activity of CTL-A against elastase, along with its cellular safety and well-established synthetic route, warrants further investigation of CTL-A as a candidate against COVID-19 pathogeneses.

High-power, short-duration ablation in the coronary sinus: clinical cases and preliminary observations on swine hearts.

PURPOSE: Coronary sinus-related arrhythmias are common; however, it is difficult to perform radiofrequency (RF) ablation at these sites efficiently and safely. High-power, short-duration ablation (HPSD) is a proven alternative strategy for pulmonary vein isolation (PVI); whether it can be applied to ablation of the coronary sinus is unknown. The purpose of this preliminary study was to evaluate the feasibility and safety of HPSD ablation in the coronary sinus. METHODS: Firstly, we demonstrated 4 clinical cases of 3 types of arrhythmias who had unsuccessful ablation with standard power initially, but received successful ablations with HPSD. Secondly, RF ablation was performed in the coronary sinus ostium (CSO) and middle cardiac vein (MCV) of 4 in vitro swine hearts. Two protocols were compared: HPSD (45 W/5 S×5 rounds) and a conventional strategy that used low-power, long-duration ablation (LPLD: 25 W/10 S ×5 rounds). The total duration of HPSD protocol was 25 s, and which of LPLD was 50 s. RESULTS: A total of 28 lesions were created. HPSD can produce longer, wider, deeper, and larger lesions than LPLD. This difference was more pronounced when the ablation was in the MCV. One instance of steam pop occurred during LPLD in the MCV. CONCLUSIONS: HPSD is an effective alternative strategy for ablation in coronary sinus according to clinical applications and preliminary animal study. However, the safety needs to be further evaluated based on more animal and clinical studies.

Low-Level Stimulation and Ethanol Ablation of the Vein of Marshall Prevent the Vagal-Mediated AF.

Background: The mechanisms for the vein of Marshall (VOM) mediated atrial fibrillation (AF) are not completely understood. We sought to evaluate the contribution of the intrinsic cardiac autonomic nervous system in VOM mediated AF. Method: Seven mongrel dogs were administered propranolol and continuously exposed to left superior ganglionated plexi (LSGP) stimulation, LSGP + low-level VOM stimulation, LSGP + atropine administration, LSGP + VOM filling with ethanol separately. The effective refractory period (ERP) and window of vulnerability (WOV) at the left superior pulmonary vein (LSPV), left inferior pulmonary vein (LIPV) and left atrial appendage (LAA) were measured. Result: LSGP stimulation significantly shortens the ERP and prolonged the ERP dispersion and WOV in LSPV, LIPV, and LAA. Interestingly, low-level VOM stimulation, atropine administration, or VOM filling with ethanol were able to attenuate the effects of LSGP in all sites. Conclusion: VOM as an inter-communication pathway of ganglionated plexis plays an important role in the development of vagal-related AF.

E/E' Is a New Independent Predictor of Recovered Ejection Fraction in Patients With Systolic Heart Failure Undergoing Ablation for Atrial Fibrillation.

Aims: Catheter ablation should be considered in patients with atrial fibrillation (AF) and with heart failure (HF) with reduced ejection fraction (EF; HFrEF) to improve survival and reduce heart failure hospitalization. Careful patient selection for AF ablation is key to achieving similar outcome benefits. However, limited data exist regarding predictors of recovered ejection fraction. We aimed to evaluate the predictors of recovered ejection fraction in consecutive patients with HF undergoing AF ablation. Methods and Results: A total of 156 patients [67.3% men, median age 63 (11)] with AF and HF underwent initial catheter ablation between September 2017 and October 2019 in the First Affiliated Hospital of Dalian Medical University. Overall, the percentage of recovered ejection fractions was 72.3%. Recovered EFs were associated with a 39% reduction in all-cause hospitalization compared to non-recovered EFs at the 1-year follow-up [23.8 vs. 62.8 (odds ratio) OR 2.09 (1.40-3.12), P < 0.001]. Univariate analysis for recovered EFs showed that diabetes (P = 0.083), prevalent HF (P = 0.014), prevalent AF (P = 0.051), LVEF (P = 0.022), and E/E' (P = 0.001) were associated with EF improvement. Multivariate analysis showed that the only independent predictor of EF recovery was E/E' [OR 1.13 (1.03-1.24); P = 0.011]. A receiver operating characteristic analysis determined that the suitable cut-off value for E/E' was 15 (sensitivity 38.7%, specificity 89.2%, the area under curve 0.704). Conclusions: Ejection fraction (EF) recovery occurred in 72.3% of patients, associated with a 39% reduction in all-cause hospitalization compared to the non-recovered EFs in our cohort. The only independent predictor of recovered EF was E/E' < 15 in our series.

High efficiency and workflow of His bundle pacing and atrioventricular node ablation guided by three-dimensional mapping system.

BACKGROUND: Atrioventricular node (AVN) ablation combined with His bundle pacing is an effective strategy for permanent atrial fibrillation (AF) with rapid ventricular rate refractory to pharmacological therapy. We aimed to access the feasibility and efficiency of His bundle pacing and AVN ablation guided by three-dimensional (3-D) mapping system throughout the procedure. METHODS: Eighteen patients with permanent AF with refractory rate and symptoms were referred for His bundle pacing and AVN ablation guided by 3-D mapping (CARTO3). Electroanatomic 3-D mapping of the right atrium and right ventricle was performed by the ablation catheter with CARTO 3 system, followed by the visualization of the leads for implantation and AVN ablation. RESULTS: Implantation of His bundle and ventricular leads and AVN ablation were achieved successfully with the help of 3-D mapping in 17 patients. Selective His bundle pacing was achieved in five patients (29.4%), and the other (70.6%) were nonselective His bundle pacing. The mean procedure duration was 99.4 ± 16.4 minutes. The mean fluoroscopy time was 7.0 ± 2.6 minutes. The time spent on His lead implantation was 6.1 ± 3.2 minutes. One patient experienced AVN ablation from left side under aortic valves due to no effect of ablation in right atrium. CONCLUSION: His bundle pacing and AVN ablation guided by throughout real-time 3-D mapping system are of high-efficiency and feasibility.

Chemical modification of ovatodiolide revealed a promising amino-prodrug with improved pharmacokinetic profile.

Stepwise modification of ovatodiolide revealed a prodrug, NMP-diepoxyovatodiolide, which can provide sustained release of an active compound, substantial metabolic stability and a unique accumulation profile in the liver. Besides, NMP-diepoxyovatodiolide demonstrated therapeutic benefits in an acute autoimmune hepatitis mouse model and a broad safety window. Therefore, NMP-diepoxyovatodiolide is a very promising candidate for further development of liver-related drugs.