Isolation of cadmium-resistance and siderophore-producing endophytic bacteria and their potential use for soil cadmium remediation.

Endophyte-assisted phytoremediation is an emerging technique for soil heavy metals (HMs) remediation and has become a research focus in the world because of the benefits of endophytes on plant growth and uptake of HMs. In this study, multifunctional endophytic bacteria strains were isolated and screened, and the feasibility of these strains for soil cadmium (Cd) remediation was investigated by soil incubation experiments and pot experiments. All endophytic bacteria were isolated from the roots of woody plants grown on Cd-contaminated soil. Seven endophytic bacteria strains had capacities to tolerate Cd toxicity and produce siderophores, and sequence analysis of the 16S rRNA gene classified these strains as belonging to the genera Burkholderia, Pseudomonas, Pantoea, and Herbaspirillum. All strains were able to produce hydroxamate siderophores (32.40%-91.49%) and had three or more plant growth promoting properties such as phosphorus solubilization, nitrogen fixation, indole acetic acid and 1-aminocyclopropane-1-carboxylate deaminase production. They were all strongly resistant to Cd2+ toxicity, with the minimum inhibitory concentration in LB medium ranging from 1.5 mM to 9.0 mM. Except for strain Burkholderia contaminans JLS17, other strains showed decreasing removal rates within continuously elevated Cd2+ concentration of 10-100 mg L-1. Compared with the uninoculated treatment, the inoculation of strains B.contaminans JLS17, Pseudomonas lurida JLS32, and Pantoea endophytica JLS50 effectively increased the concentration of acid-soluble Cd and decreased the concentration of reducible, oxidizable, and residual Cd in the soils of different Cd contamination levels. In pot experiments, inoculation of strains JLS17 and YTG72 significantly (p < 0.05) promoted the growth of above-ground parts and root system of slash pine (Pinus elliottii) under Cd stress. This study provides a valuable biological resource for endophyte-assisted phytoremediation and a theoretical basis for the application of endophytic bacteria for remediation of Cd-contaminated soil.

Untargeted metabolomics reveal the metabolic profile of normal pulmonary circulation.

BACKGROUND: As an important place of material exchange, the homeostasis of the pulmonary circulation environment and function lays an essential foundation for the normal execution of various physiological functions of the body. Small metabolic molecules in the circulation can reflect the corresponding state of the pulmonary circulation. METHODS: We enrolled patients with Patent Foramen Ovale and obtained blood from the pulmonary arteries and veins through heart catheterization. UPLC-MS based untargeted metabolomics was used to compare the changes and metabolic differences of plasma between pulmonary vein and pulmonary artery. RESULTS: The plasma metabolomics revealed that pulmonary artery had a different metabolomic profile compared to venous. 1060 metabolites were identified, and 61 metabolites were differential metabolites. Purine, Amino acids, Nicotinamide, Tetradecanedioic acid and Bile acid were the most markedly. CONCLUSION: The differential metabolites are mostly related to immune inflammation and damage repaired. It is suggested that the pulmonary circulation is always in a steady state of injury and repair while pathological changes may be triggered when the homeostasis is broken. These changes play an important role in revealing the development process and etiology of lung homeostasis and related diseases. Relevant metabolites can be used as potential targets for further study of pulmonary circulation homeostasis.

Frequency and Size of In Situ Thrombus Within Patent Foramen Ovale.

BACKGROUND: High-resolution optical coherence tomography can detect in situ thrombi within patent foramen ovale (PFO), which can become a dangerous embolic source. This study aimed to investigate the frequency and size of in situ thrombus within PFO using optical coherence tomography. METHODS: The cross-sectional study was conducted at Fuwai Hospital (Beijing, China) between 2020 and 2021. From 528 consecutive patients with PFO, 117 (age, 34.33 [SD, 11.30] years) without known vascular risk factors were included; according to PFO-related symptoms, they were divided into the stroke (n=43, including 5 patients with transient ischemic attack), migraine (n=49) and asymptomatic (n=25) groups. Optical coherence tomography was used to evaluate in situ thrombi and abnormal endocardium within PFO. Univariable analysis and a logistic model were used to evaluate the association between stroke and in situ thrombus; age, sex, body mass index, and antithrombotic therapy were included as covariates. RESULTS: Antithrombotic therapy was used more frequently in the stroke group than in the migraine group (76.7% versus 12.2%; P<0.001). In situ PFO thrombi were detected in 36 (83.7%), 28 (57.1%), and 0 (0.0%) patients from the stroke, migraine, and asymptomatic groups, respectively (P<0.001). Between the stroke and migraine groups, there was no significant difference in the median (interquartile range) thrombus number per patient (7 [3-12] versus 2 [0-10]; P=0.199), maximum thrombus diameter (0.35 [0.20-0.46] versus 0.21 [0-0.68] mm; P=0.597), or total thrombus volume (0.02 [0.01-0.05] versus 0.01 [0-0.05] mm3; P=0.386). Additionally, in situ thrombus was significantly associated with stroke risk (odds ratio, 4.59 [95% CI, 1.26-16.69]). Abnormal endocardium within PFO occurred in patients with in situ thrombi (71.9%) but not in those without. During optical coherence tomography examination, migraine occurred in 2 patients with in situ thrombi. CONCLUSIONS: The frequency of in situ thrombus was extremely high in stroke and migraine groups, while none of the asymptomatic individuals presented with an in situ thrombus. In situ thrombus formation may play a role in patients with PFO-associated stroke or migraines and have therapeutic implications. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04686253.

Interventional Occlusion of Large Patent Ductus Arteriosus in Adults with Severe Pulmonary Hypertension.

(1) Background: the indications for transcatheter closure of large patent ductus arteriosus (PDA) with severe pulmonary hypertension (PH) are still unclear, and scholars have not fully elucidated the factors that affect PH prognosis. (2) Methods: we retrospectively enrolled 134 consecutive patients with a PDA diameter ≥10 mm or a ratio of PDA and aortic >0.5. We collected clinical data to explore the factors affecting follow-up PH. (3) Results: 134 patients (mean age 35.04 ± 10.23 years; 98 women) successfully underwent a transcatheter closure, and all patients had a mean pulmonary artery pressure (mPAP) >50 mmHg. Five procedures were deemed to have failed because their mPAP did not decrease, and the patients experienced uncomfortable symptoms after the trial occlusion. The average occluder (pulmonary end) size was almost twice the PDA diameter (22.33 ± 4.81 mm vs. 11.69 ± 2.18 mm). Left ventricular end-diastolic dimension (LVEDD), mPAP, and left ventricular ejection fraction (LVEF) significantly reduced after the occlusion, and LVEF recovered during the follow-up period. In total, 42 of the 78 patients with total pulmonary resistance >4 Wood Units experienced clinical outcomes, and all of them had PH in the follow-up, while 10 of them had heart failure, and 4 were hospitalized again because of PH. The results of a logistic regression analysis revealed that the postoperative mPAP had an independent risk factor (odds ratio = 1.069, 95% confidence interval: 1.003 to 1.140, p = 0.040) with a receiver operating characteristic curve cut-off value of 35.5 mmHg (p < 0.001). (4) Conclusions: performing a transcatheter closure of large patent ductus arteriosus is feasible, and postoperative mPAP was a risk factor that affected the follow-up PH. Patients with a postoperative mPAP >35.5 mmHg should be considered for targeted medical therapy or should undergo right heart catheterization again after the occlusion.

68Ga-FAPI PET/CT for molecular assessment of fibroblast activation in right heart in pulmonary arterial hypertension: a single-center, pilot study.

BACKGROUND: Positron emission tomography (PET) imaging with radiolabeled fibroblasts activation protein inhibitor (FAPI) provides the opportunity to directly visualize fibrosis. This study aimed to investigate the feasibility of 68Ga-FAPI PET imaging in assessing right ventricular (RV) fibrotic remodeling and the relationship between FAPI uptake with parameters of pulmonary hemodynamics and cardiac function in pulmonary arterial hypertension (PAH) patients. METHODS: In this pilot study, sixteen PAH patients were enrolled to participate in cardiac 68Ga-FAPI PET/CT imaging. All patients underwent right heart catheterization and echocardiography for assessment of pulmonary hemodynamics and cardiac function within seven days. Cardiac FAPI uptake was visually assessed and quantified as maximum standardized uptake value (SUVmax). RESULTS: Twelve PAH patients exhibited FAPI uptake in RV free wall and insertion point. The overall activity of FAPI accumulated in the RV free wall (SUVmax: 2.5 ± 1.8, P < 0.001) and insertion point (SUVmax:2.5 ± 1.7, P < 0.001) was significantly upregulated compared to left ventricle (SUVmax:1.5 ± 0.5). Patients with tricuspid annular plane systolic excursion (TAPSE) < 17 mm presented significantly higher uptake than those with TAPSE ≥ 17 mm in both RV free wall (SUVmax: 3.4 ± 1.9 vs 1.7 ± 1.1, P = 0.010) and insertion point (SUVmax: 3.4 ± 1.9 vs 1.6 ± 0.7, P = 0.028), indicating RV uptake of FAPI was associated with RV dysfunction. There was significant positive correlation between cardiac FAPI uptake and total pulmonary resistance and the level of N-terminal pro b-type natriuretic peptide. CONCLUSIONS: 68Ga-FAPI PET/CT imaging is feasible to directly visualize fibrotic remodeling of RV in patients with PAH.

Is combined use of radiofrequency ablation and balloon dilation the future of interatrial communications?

INTRODUCTION: Personalized and stable interatrial communication is an important palliative therapy for patients with heart failure. However, this remains a technically challenging task. AREAS COVERED: In the past decades, substantial advancements in atrial septostomy for the creation of controllable and durable interatrial communication have been made, and numerous novel devices and techniques are in various stages of development. In this review, we discuss the evolving indications for atrial septostomy, current approaches with or without device implantation, and indicators for optimal interatrial communication. The combined use of radiofrequency ablation and balloon dilation (CURB) is an individualized management approach based on underlying hemodynamics, which demonstrates unique advantages in creating a sufficient interatrial communication with satisfactory stability. The advantages and disadvantages of this implant-free procedure are analyzed and its clinical prospects are assessed. EXPERT OPINION: With ready availability, high safety, and efficacy, CURB is a promising procedure for creating personalized and stable interatrial communication without device implantation. Further research is required to simplify the procedure, screen optimal reference parameters for personalized therapy, and evaluate the long-term outcome in a large population of patients.

Transcatheter closure of inferior sinus venosus defect using a patent ductus arteriosus occluder following simulation with a 3D-printed model.

Background: Transcatheter closure of inferior sinus venosus defect (ISVD) is still contraindication. To explore whether transcatheter closure with patent ductus arteriosus (PDA) occluders is possible for ISVD. Methods: From June 2014 to March 2021, 12 patients were recruited diagnosed as <25 mm ISVD. The three-dimensional printing (3DP) heart model was produced based on multi-slice computed tomography (MSCT) scans. Preoperative closure simulation was planned on the personalized 3D model for each patient. Follow-up including electrocardiography (ECG), transthoracic echocardiography (TTE), and X-ray was traced. Results: 3DP models of 12 patients were successfully printed. Twelve patients had been diagnosed with <25 mm ISVD and 4 of them had another secundum atrial septal defect (ASD). All patients were produced interventional therapy successfully. PDA occluder was implanted to closed ISVD, and ASD was closed using ASD occluder simultaneously. The average diameter of ISVD measured by TTE was (12.67±3.80), and the average diameter of sagittal axes and longitudinal axes measured by the 3D-printed model was (17.08±3.20) and (18.42±4.62) mm, respectively. The average size of PDA (diameter of pulmonary artery side) was (28.17±3.35) mm. Compared with the preoperative, the X-ray cardiothoracic ratio (0.51±0.04 vs. 0.47±0.06, P=0.007) and the right ventricle anterior-posterior diameter (31.17±5.65 vs. 24.58±3.75 mm, P<0.001) of postoperative was significantly decreased. During the average (47.75±27.52) months follow-up, it has achieved satisfying results, and there were no severe adverse events such as device transposition, death, and pericardial tamponade occurred. Conclusions: Assisting by 3D heart model, transcatheter closure of ISVD with PDA occluder had an excellent outcome. This method provides a new considerable treatment strategy for ISVD.

First in-human modified atrial septostomy combining radiofrequency ablation and balloon dilation.

OBJECTIVE: Preclinical research suggests that the combined use of radiofrequency ablation and balloon dilation (CURB) could create stable interatrial communications without device implantation. This study examined the first in-human use of CURB for modified atrial septostomy in patients with severe pulmonary arterial hypertension (PAH). METHODS: Between July 2018 and October 2021, CURB was performed in 19 patients with severe PAH (age: 31.5±9.1 years; mean pulmonary artery pressure: 73 mm Hg (IQR: 66-92); pulmonary vascular resistance: 18.7 Wood units (IQR: 17.8-23.3)). Under guidance of intracardiac echocardiography and three-dimensional location system, (1) fossae ovalis was reconstructed and ablated point-by-point with radiofrequency; (2) then graded balloon dilation was performed after transseptal puncture and the optimal size was determined according to the level of arterial oxygen saturation (SatO2); (3) radiofrequency ablation was repeated around the rims of the created fenestration. The interatrial fenestrations were followed-up serially. RESULTS: After CURB, the immediate fenestration size was 4.4 mm (IQR: 4.1-5.1) with intracardiac echocardiography, systolic aortic pressure increased by 10.2±6.9 mm Hg, cardiac index increased by 0.7±0.3 L/min/m2 and room-air resting SatO2 decreased by 6.2±1.9% (p<0.001). One patient experienced increased pericardiac effusion postoperatively; the others had no complications. On follow-up (median: 15.5 months), all interatrial communications were patent with stable size (intraclass correlation coefficient=0.96, 95%CI:0.89 to 0.99). The WHO functional class increased by 1 (IQR: 1-2) (p<0.001) with improvement of exercise capacity (+159.5 m, P<0.001). CONCLUSION: The interatrial communications created with CURB in patients with severe PAH were stable and the mid-term outcomes were satisfactory. TRIAL REGISTRATION NUMBER: NCT03554330.

Ventilation/perfusion imaging predicts response to balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.

OBJECTS: Although balloon pulmonary angioplasty (BPA) has emerged as an alternative treatment option for chronic thromboembolic pulmonary hypertension (CTEPH), it is followed in some patients by residual PH. We studied the efficacy of BPA on pulmonary blood flow and the predictive value of ventilation/perfusion (V/Q) scanning. METHODS: We retrospectively reviewed the clinical database, which included patients diagnosed with CTEPH who had received BPA. All patients undergone V/Q scanning to quantify the extent of pulmonary perfusion abnormality before and after BPA. Pulmonary hemodynamics were assessed by right heart catheterization, and cardiac function and exercise capacity were evaluated at baseline and post-BPA. A total of 120 CTEPH patients were included for analysis. RESULTS: BPA significantly alleviated mean pulmonary arterial pressure (mPAP: 48.0 ± 12.9 mmHg vs 34.7 ± 10.3 mmHg, P < 0.001) and pulmonary vascular resistance (PVR: 8.8 ± 4.1 Wood units vs 5.2 ± 3.0 Wood units, P < 0.001), and improved cardiac function (N-terminal pro B-type natriuretic peptide: 1628.7 ± 2887.2 pg/mL vs 400.4 ± 669.3 pg/mL, P < 0.001) and exercise capacity (6-minute walking distance: 386 ± 122 m vs 461 ± 86 m, P < 0.001). The extent of pulmonary perfusion abnormality represented by the percentage of perfusion defects (PPDs%) was improved after BPA (50.1 ± 13.6 vs 35.6 ± 14.2, P < 0.001), with the right and inferior lung lobes benefitting the most. PPDs% < 35.5 at baseline and greater restoration of PPDs% after BPA (∆PPDs% > 20.6) were associated with a better response to BPA (PPDs% < 35.5: odds ratio [OR] 10.857, 95% confidence interval [95%CI] 1.393-84.635, P = 0.023; ∆PPDs% > 20.6: OR 1.035, 95% CI 1.002-1.068, P = 0.036). CONCLUSION: BPA significantly restored pulmonary blood flow, predominantly in the right and inferior lobes. V/Q scanning has the potential to predict the therapeutic response to BPA for CTEPH.

Transcatheter Closure of Patent Ductus Arteriosus via Different Approaches.

Background: There have been marked advances in devices such as Amplatzer Duct Occluder II (ADO-II) or vascular plug through 5Fr delivery sheath for closure of patent ductus arteriosus (PDA) in the past five decades, making it possible for cardiologists to deliver occluders via different approaches. However, comparisons of these different approaches have not been reported. Therefore, the aim of this study was to summarize and compare the advantages of different approaches for PDA closure, and to guide clinical strategies. Methods: This retrospective study included all patients undergoing transcatheter closure of PDA from 2019 to 2020. Patients were matched by 1:1 propensity score matching (PSM). The retrograde femoral artery approach (FAA) and simple vein approach (SVA) groups were compared with the conventional arteriovenous approach (CAA). Results: The average age of the 476 patients was 21.05 ± 21.15 years. Their average weight was 38.23 ± 24.1 kg and average height was 130.14 ± 34.45 cm. The mean diameter of the PDA was 4.29 ± 2.25 mm. There were 127 men and 349 women, comprising 205 adults and 271 children. Among them, 197 patients underwent CAA, 223 underwent SVA, and 56 underwent retrograde FAA. The diameter in the FAA group was smaller than that in the other two groups, but was similar in adults and children. In the PSM comparison of CAA and SVA, 136 patients with CAA and 136 patients with SVA were recruited. Simple vein approach was associated with markedly reduced length of hospital stay, length of operation, and contrast medium usage as compared with CAA (all P < 0.05). In the PSM comparison of FAA and CAA, 30 patients with CAA and 30 patients with FAA were recruited. The operation duration was longer in the CAA than in the FAA group. There were no significant differences in postoperative complications among groups. Conclusion: Patent ductus arteriosus closure by using the SVA and FAA is safe and effective, and has certain advantages in some respects as compared with CAA.

Combination of F-ASO and Targeted Medical Therapy in Patients With Secundum ASD and Severe PAH.

OBJECTIVES: This study was conducted to investigate the combined use of fenestrated atrial septal occluder (F-ASO) and targeted medical therapy (TMT) in patients with secundum atrial septal defect (ASD) and severe pulmonary arterial hypertension (PAH). BACKGROUND: Treatment of patients with ASD and severe PAH is still challenging. METHODS: After ethical approval was obtained, 56 consecutive patients with ASD with severe PAH were included (7 men, 49 women; median age 50.5 years; mean ASD size 26.9 ± 4.6 mm). After 3 months of TMT, transcatheter closure was performed using F-ASO in patients with ratios of pulmonary to systemic blood flow ≥1.5. TMT was continued post-operatively together with 6 months of dual-antiplatelet therapy. The hemodynamic variables during baseline, TMT alone, and combined treatment with F-ASO were compared. RESULTS: After only TMT, systolic pulmonary arterial pressure (-14.5 mm Hg; p < 0.001), pulmonary vascular resistance (-3.9 Wood units; p < 0.001), and exercise capacity (+72.0 m; p < 0.001) improved. Ratio of pulmonary to systemic blood flow increased by 0.9 (p < 0.001), with adverse cardiac remodeling (right ventricular dimension +3.5 mm; p < 0.001). Closure with F-ASO (median size 34.0 mm) led to further decrease in systolic pulmonary artery pressure (-6.0 mm Hg; p < 0.001). Follow-up (median duration 10 months) revealed further improvement in exercise capacity (+60.5 m; p < 0.001), with favorable cardiac remodeling (right ventricular dimension -9.9 mm; p < 0.001). In addition, all fenestrations were stable (p = 0.699), with negligible shunt (median ratio of pulmonary to systemic blood flow 1.1) and no complications. One year later, pulmonary artery pressure was normalized in 8 of 19 patients, and PAH recurred in 5 patients after discontinuation of TMT. CONCLUSIONS: In patients with ASD and severe PAH, combination of F-ASO and TMT was a safe and effective procedure. Compared with TMT alone, the combined treatment further improved exercise capacity, with favorable cardiac remodeling.

Transfemoral transcatheter puncture of interventricular septum in a swine model: A novel transfemoral-venous access to left ventricle with the assistance of arterio-venous circuit.

OBJECTIVE: Via subclavian/jugular vein, successful puncture of interventricular septum (IVS) has been achieved transvenously. However, the approach was limited by acute entry-angle. The study was conducted to investigate a novel transcatheter puncture of IVS via femoral access and transfemoral-venous access to left ventricle (LV) through IVS. METHODS: Via femoral artery, transcatheter puncture of mid-IVS was performed with a custom-made nickel-titanium needle and 6F-sheath in 16 healthy mini-swine. Then femoral arterio-venous circuit was established through IVS. After pre-dilation of IVS, a 20F-sheath was introduced into LV transvenously over-the-guidewire in 15 swine. Furthermore, transfemoral-venous TAVR was attempted with the approach in another swine. IVS was evaluated postoperatively and was further confirmed pathologically 2 months later. RESULTS: All transcatheter puncture of IVS was performed successfully in LV and the mid-IVS thickness was 7.67 ± 0.98 mm. In all swine, femoral arterio-venous circuit was established via IVS, and a 20F-sheath was introduced into LV and aorta transfemoral-venously (entry-angle: 145.3 ± 12.2° in front view). After the procedure, there was one swine with moderate tricuspid-regurgitation and five swine with mild residual-shunt (2.6 ± 0.7 mm). Two months later, residual-shunt was still detected in three swine and the communication was confirmed pathologically. In other swine, no defect occurred and replacement-scar was identified along puncture-tract. In the swine underwent transfemoral-venous TAVR, prosthetic valve was deployed successfully with good function. CONCLUSIONS: Transfemoral transcatheter puncture of IVS is feasible and safe in a swine model, and large sheath can be introduced into LV transfemoral-venously using the novel access with the aid of vessel circuit.