Purification, crystallization and preliminary crystallographic analysis of Chlamydophila pneumoniae AP endonuclease IV.

Base excision is a crucial DNA repair process mediated by endonuclease IV in nucleotide excision. In Chlamydia pneumoniae, CpendoIV is the exclusive AP endonuclease IV, exhibiting DNA replication error-proofreading capabilities, making it a promising target for anti-chlamydial drug development. Predicting the structure of CpendoIV, molecular docking with DNA was performed, analyzing complex binding sites and protein surface electrostatic potential. Comparative structural studies were conducted with E. coli EndoIV and DNA complex containing AP sites.CpendoIV was cloned, expressed in E. coli, and purified via Ni-NTA chelation and size-exclusion chromatography. Low NaCl concentrations induced aggregation during purification, while high concentrations enhanced purity.CpendoIV recognizes and cleaving AP sites on dsDNA, and Zn2+ influences the activity. Crystallization was achieved under 8% (v/v) Tacsimate pH 5.2, 25% (w/v) polyethylene glycol 3350, and 1.91 Å resolution X-ray diffraction data was obtained at 100 K. This research is significant for provides a deeper understanding of CpendoIV involvement in the base excision repair process, offering insights into Chlamydia pneumoniae.

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.

Efficacy and safety of a parylene-coated occluder for atrial septal defect: a prospective, multi-center, randomized controlled clinical trial.

BACKGROUND: Nitinol-containing devices are widely used in clinical practice. However, there are concerns about nickel release after nitinol-containing device implantation. This study aimed to compare the efficacy and safety of a parylene-coated occluder vs. a traditional nitinol-containing device for atrial septal defect (ASD). METHODS: One-hundred-and-eight patients with ASD were prospectively enrolled and randomly assigned to either the trial group to receive a parylene-coated occluder (n = 54) or the control group to receive a traditional occluder (n = 54). The plugging success rate at 6 months after device implantation and the pre- and post-implantation serum nickel levels were compared between the two groups. A non-inferiority design was used to prove that the therapeutic effect of the parylene-coated device was non-inferior to that of the traditional device. The Cochran-Mantel-Haenszel chi-squared test with adjustment for central effects was used for the comparison between groups. RESULTS: At 6 months after implantation, successful ASD closure was achieved in 52 of 53 patients (98.11%) in both the trial and control groups (95% confidence interval (CI): [-4.90, 5.16]) based on per-protocol set analysis. The absolute value of the lower limit of the 95% CI was 4.90%, which was less than the specified non-inferiority margin of 8%. No deaths or severe complications occurred during 6 months of follow-up. The serum nickel levels were significantly increased at 2 weeks and reached the maximum value at 1 month after implantation in the control group (P < 0.05 vs. baseline). In the trial group, there was no significant difference in the serum nickel level before vs. after device implantation (P > 0.05). CONCLUSIONS: The efficacy of a parylene-coated ASD occluder is non-inferior to that of a traditional uncoated ASD occluder. The parylene-coated occluder prevents nickel release after device implantation and may be an alternative for ASD, especially in patients with a nickel allergy.

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.

Off-label use of duct occluder in transcatheter closure of secundum atrial septal defect with no rim to right pulmonary vein.

OBJECTIVE: Transcatheter closure is usually contraindicated in secundum atrial septal defect with no rim to right pulmonary vein. The morphology of an atrial septal defect is special in these patients, and the off-label use of a duct occluder might make transcatheter closure possible with the assistance of a personalized heart model. However, the related data are absent. This study was performed to investigate the off-label use of a duct occluder in the transcatheter closure of an atrial septal defect with no right pulmonary vein rim. METHODS: Seven consecutive patients with an atrial septal defect (2 male/5 female; 40.1 ± 15.2 years) with no right pulmonary vein rim were referred for attempted transcatheter closure, and a personalized heart model was produced on the basis of multislice computed tomography images. With the elastic heart model, in vitro trial occlusion was performed with a duct occluder for preoperative evaluation, and the results were compared with postoperative outcomes. RESULTS: A single atrial septal defect was identified in 6 patients, and a double atrial septal defect was identified in another patient (1 atrial septal defect with no right pulmonary vein rim and 1 with sufficient surrounding rims). The size of the atrial septal defect was 13.4 ± 2.2 mm, and the in vitro balloon-stretched diameter was 20.2 ± 3.2 mm in the heart model. In vitro trial occlusion was achieved in all patients, and subsequent in vivo transcatheter closure was performed successfully with the duct occluder of the same size (24.3 ± 3.1 mm). During follow-up (1.57 ± 0.84 years), mild pericardial effusion was identified in 2 patients and disappeared within 3 months. No other complications occurred. CONCLUSIONS: By using a personalized heart model, the off-label use of a duct occluder is feasible and safe in the transcatheter closure of an atrial septal defect with no right pulmonary vein rim. Further research is required to evaluate the long-term outcomes.

Outcomes of Percutaneous Closure of Patent Ductus Arteriosus Accompanied With Unilateral Absence of Pulmonary Artery.

BACKGROUND: Limited data have reported the outcomes of percutaneous closure of patent ductus arteriosus (PDA) in patients with unilateral absence of pulmonary artery (UAPA). This study aimed to evaluate the symptomatology, diagnosis and therapy, especially the transcatheter closure of PDA in patients with PDA associated with UAPA. MATERIALS AND METHODS: Patients diagnosed with PDA and UAPA were retrospectively enrolled from August 2010 through January 2016. Clinical data, treatment and follow-up information were evaluated. RESULTS: Thirteen patients (6 males and 7 females) were diagnosed with PDA associated with UAPA. Percutaneous closure was successfully conducted in 6 patients successfully. The median age was 7 years (7 months to 37 years). The mean diameter of the PDA and occluders were 4.7 ± 1.8mm (2-7mm) and 11.3 ± 3.9mm (6-14mm), respectively. The mean pulmonary artery pressure was 41.5 ± 13.5mmHg (25-62mmHg). The diameter of PDA has no relationship with the degree of pulmonary artery pressure (r = 0.239, P = 0.648). In 4 patients, systolic pulmonary arterial pressure decreased significantly after closure with 69.0 ± 10.7 versus 48.0 ± 11.3mmHg (P = 0.146), and also the mean pulmonary arterial pressure was 54.5 ± 5.7 mm Hg versus 30.5 ± 3.9mmHg (P = 0.04). In all, 1 patient had a trace residual shunt, which disappeared within 24 hours. CONCLUSIONS: In appropriate patients with PDA associated with UAPA, transcatheter closure of PDA has the potential to improve the pulmonary artery hypertension. Further follow-up is required to monitor the long-term outcomes.

Simultaneous Transcatheter Closure of Multiple Atrial Septal Defects Using Dual Amplatzer Septal Occluder Devices.

BACKGROUND: Transcatheter closure has been a recognised treatment strategy for multiple atrial septal defects (mASDs). This study aimed to examine the feasibility, effectiveness, and safety of transcatheter closure of mASDs using dual Amplatzer septal occluder (ASO) devices. METHODS: We retrospectively reviewed 34 patients who underwent transcatheter closure of mASDs using dual ASO devices from April 2005 to December 2014. RESULTS: Eight men and 26 women who successfully underwent transcatheter closure of mASDs were included. Ten (29.4%) patients had 3 defects or more. The mean diameters of the larger and smaller defects were 14.0±3.9 mm (8-20 mm) and 9.1±2.6 mm (4-15 mm), respectively. The mean diameters of the larger and smaller devices were 22.2±4.8 mm (13-30 mm) and 17.3±4.1 mm (10-26 mm), respectively. Devices were deployed by the "sandwiches" technique or an interleaved pattern. Immediately after the procedure, 23 (67.6%) patients had complete closure and 11 patients had a residual shunt (6 trivial, 3 small, 1 moderate, 1 large). During the 6 months of follow-up, 30 (88.2%) patients had complete closure of the shunt and 4 patients had a residual shunt (1 large, 3 small). Complications included 2 cases of pericardial effusion, which disappeared at 3 months. CONCLUSIONS: Simultaneous device implantation in transcatheter closure of mASDs is feasible and effective. The incidence rate of residual shunts is slightly high in the short term, but tends to decrease during mid-term follow-up.

A feasible method for non-invasive measurement of pulmonary vascular resistance in pulmonary arterial hypertension: Combined use of transthoracic Doppler-echocardiography and cardiac magnetic resonance. Non-invasive estimation of pulmonary vascular resistance.

BACKGROUND: Transthoracic Doppler-echocardiography (TTE) can estimate mean pulmonary arterial pressure (MPAP) and pulmonary capillary wedge pressure (PCWP) reliably, and cardiac magnetic resonance (CMR) is the best modality for non-invasive measurement of cardiac output (CO). We speculated that the combined use of TTE and CMR could provide a feasible method for non-invasive measurement of pulmonary vascular resistance (PVR) in pulmonary arterial hypertension (PAH). METHODS AND RESULTS: Right heart catheterization (RHC) was undertaken in 77 patients (17M/60F) with PAH, and simultaneous TTE was carried out to evaluate MPAP, PCWP and CO. Within 2 days, CO was measured again with CMR in similar physiological status. Then, PVR was calculated with the integrated non-invasive method: TTE-derived (MPAP-PCWP)/CMR-derived CO and the isolated TTE method: TTE-derived (MPAP-PCWP)/TTE-derived CO, respectively. The PVR calculated with integrated non-invasive method correlated well with RHC-calculated PVR (r = 0.931, 95% confidence interval 0.893 to 0.956). Between the integrated non-invasive PVR and RHC-calculated PVR, the Bland-Altman analysis showed the satisfactory limits of agreement (mean value: - 0.89 ± 2.59). In comparison, the limits of agreement were less satisfactory between TTE-calculated PVR and RHC-calculated PVR (mean value: - 1.80 ± 3.33). Furthermore, there were excellent intra- and inter-observer correlations for the measurements of TTE and CMR (P < 0.001 for all). CONCLUSIONS: The combined use of TTE and CMR provides a clinically reliable method to determine PVR non-invasively. In comparison with RHC, the integrated method shows good accuracy and repeatability, which suggests the potential for the evaluation and serial follow-up in patients with PAH. TRANSLATIONAL PERSPECTIVE: In PAH, the non-invasive measurement of PVR is very important in clinical practice. Up to now, however, the widely accepted non-invasive method is still unavailable. Since TTE can estimate (MPAP-PCWP) reliably and CMR is the best image modality for the measurement of CO, the combined use of two modalities has the potential to determine PVR non-invasively. In this research, the integrated non-invasive method showed good diagnostic accuracy and repeatability compared with RHC. Therefore, it might be a feasible method for non-invasive measurement of PVR in patients with PAH.

Use of covered Cheatham-Platinum stent as the primary modality in the treatment for native coarctation of the aorta.

BACKGROUND: Bare stent implantation in the treatment for native and recurrent coarctation of the aorta (CoA) has become established as an alternative to surgery and balloon angioplasty. However, this modality still encounters significant complications during the procedure and/or follow-up. The covered Cheatham-Platinum (CP) stent commonly used to be chosen as a rescue treatment in these patients. The purpose of this study was to evaluate the use of covered CP stent as the primary modality in the treatment for native CoA. METHODS: Twenty-five covered CP stents and 2 bare CP stents were implanted in 25 patients with native CoA. All patients after the intervention were invited for follow-up examinations. RESULTS: The peak systolic gradient across the lesion decreased significantly from a median value of 67.5 mmHg (quartile range, 19.3 mmHg) to 2 mmHg (quartile range, 4.0 mmHg) (P < 0.0001). Stenotic segment diameter increased from a median value of 5.0 mm (quartile range, 1.5 mm) to 17.9 mm (quartile range, 2.5 mm) (P < 0.0001). The median ratio of diameter of the coarctation postprocedure to preprocedure was 4.2 (quartile range, 1.6). All of the CP stents were placed in the suitable position without any acute complications. During a follow-up period of up to 72 months, no complications were encountered. Most of the patients (21/25) were normotensive, apart from four patients requiring antihypertensive medication during the follow-up. CONCLUSION: The implantation of covered CP stent as the primary modality is safe and effective in the treatment for native CoA in adolescents and adults.

[Value of cardiac CT examination in middle-aged and elderly patients with atrial septal defect before planned transcatheter closure].

OBJECTIVE: To investigate the value of the cardiac CT examination for decision making in middle-aged and elderly patients before planned transcatheter atrial septal defect (ASD) closure. METHODS: Cardiac CT was performed in 63 adult patients [18 males, aged from 50 to 77 years, mean age (56.87 ± 5.79) years] with ASD before planned transcatheter ASD closure. Coronary CT angiography was made for detection of associated cardiovascular diseases, followed by 3D reconstruction of ASD for determination of the defect size in the GE-workstation, results were compared between transthoracic echocardiography measurement, CT measurement, and atrial septal defect occluder waist diameter. RESULTS: Cardiac CT identified additional cardiovascular diseases in 14 patients and decision making was changed based on cardiac CT results. Coronary artery stenosis was detected in 8 patients by cardiac CT, and proved by coronary angiography, and all of them were given comprehensive management: percutaneous coronary intervention and transcatheter ASD closure were successively performed in 2 cases, and 1 case was referred to surgery for both coronary artery bypass graft and surgical ASD repair, and 5 patients were given pharmacological management for coronary artery disease besides transcatheter ASD closure. Cardiac CT identified large ASD with insufficient rim tissue in 2 cases and transcatheter closures were abandoned. Cardiac CT screened out 1 case from those with insufficient posterior inferior rim by transthoracic echocardiography, and transcatheter ASD closure was successfully performed. Cardiac CT ruled out ASD in 1 patient. In addition, cardiac CT detected 1 partial abnormal pulmonary vein connection and 1 ductus arteriosus in this cohort. A correlation on ASD measurements was found between CT size and TTE size (r = 0.80, P < 0.01; Y = 0.84X + 8.85, R(2) = 0.63, P < 0.05), and between ASO size and CT size (r = 0.92, P < 0.01;Y = 0.93X + 4.78, R(2) = 0.84, P < 0.05). CONCLUSION: In middle-aged and elderly patients with ASD for possible transcatheter closure, cardiac CT is valuable on determine ASD size and morphology and could provide incremental information for optimizing clinical management for ASD patients.

[Analysis of complications during and post interventional therapy of congenital heart disease].

OBJECTIVE: To analyze the incidence and cause of complications during and after interventional therapy for congenital heart disease (CHD). METHODS: From April 1986 to April 2009, 388 out of 6029 patients with CHD developed complications during and post interventional therapy, another 5 patients died post procedure, clinical data from these 393 patients were retrospectively analyzed. The patients with severe functional insufficiency requiring intervention or surgery during and after interventional therapy were classified as severe complications. RESULTS: The overall complication rate was 6.44% [7.69% post atrial septal defect occlusion, 4.20% post patent ductus arteriosus (PDA) occlusion, 1.31% post percutaneous balloon pulmonary valvuloplasty, 14.94% post ventricular septal defect occlusion, 3.13% post percutaneous closure of aortopulmonary collaterals, 30.95% post catheter embolotherapy of pulmonary arteriovenous malformations, 12.50% post transcatheter closure of coronary artery fistulae, 20.00% post transcatheter closure of ruptured sinus of Valsava aneurysm, 66.67% post percutaneous balloon aortic valvuloplasty]. The severe complication rate was 0.65%(39/6029). The procedure-related mortality rate was 0.08% (5/6029), 0.26% (2/761) post percutaneous balloon pulmonary valvuloplasty, 0.05% (1/2070) post PDA occlusion, 9.10% (1/11) post balloon atrial septostomy, 33.33% (1/3) post percutaneous balloon aortic valvuloplasty. Emergency Cardiovascular surgery rate was 0.22% (13/6029). Selective surgery was required in 0.13% (8/6029) of patients post procedure. Two patients (0.03%) received permanent pacemaker implantation. CONCLUSIONS: The severe complications and mortality rate of interventional therapy for CHD are relative low. Post procedure follow-up is needed fro monitoring possible procedure-related complications.

[Effects of transcatheter closure of extracardiac Fontan fenestration by Amplatzer duct or septal occluder in three patients].

OBJECTIVE: The purpose of this study was to report our experiences from the transcatheter closure of patent fenestration after total cavopulmonary connection (TCPC) with an extra cardiac conduit. METHODS: Three patients (7, 14 and 8 years old) with various forms of functionally univentricular heart lesions received a total cavopulmonary connection with an extra cardiac conduit as a final reconstructive procedure. Transcatheter occlusion of the fenestration was accomplished using a 8/6 mm Amplatzer duct occluder in one patient, and 5 mm or 10 mm Amplatzer septal occluder in the other two patients. Residual shunting following occlusion was assessed using angiography and echocardiography. RESULTS: Post total cavopulmonary connection with an extra cardiac conduit, diagnostic catheterization revealed normal pressures in the superior vena cava and pulmonary artery without obstruction at the site of the anastomosis. Angiography of the extra cardiac conduit confirmed the communication between the conduit and the atrium in all three patients and patients still suffered from cyanosis and low oxygen saturation. Immediate full occlusion of fenestration was obtained in all patients. Post closure, mean central venous pressure returned to normal accompanied with significantly increased oxygen saturation. Cyanosis was also significantly attenuated. There were no procedural complications or device failures at intra-hospital and during the 3 to 6 months follow up period. CONCLUSIONS: The Amplatzer septal or duct occluder device is a safe and effective strategy for the Fontan fenestration occlusion.

[Endovascular stent-graft repair for penetrating atherosclerotic ulcer of the descending aorta].

OBJECTIVE: To summarize the clinical experience and effectiveness of endovascular stent-graft placement for the treatment of penetrating atherosclerotic ulcer of the descending thoracic aorta. METHODS: From August 2002 to February 2006, 14 patients with penetrating atherosclerotic ulcer accepted endovascular stent-grafts placement. All patients were men, their average age was 60 years. The clinical symptoms included thoracalgia or notalgia or celiodynia (n = 13) and hemoptysis (n = 3). 11 patients had hypertension. All patients were diagnosed by CT or MRI scans. Via the cutdown on a femoral artery at local anesthesia, the stent-graft was placed after completion angiography. Then DSA examine was repeated. X-ray and EBCT or MDCT scans were performed at follow-up. RESULTS: 16 Stent-grafts were successfully placed in 14 patients, in which 2 cases were placed with two stent-grafts respectively. There were Talent stent-grafts (n = 11) and Aegis stent-grafts (n = 5). The diameter of endovascular stent-graft ranged 32 mm to 38 mm exceeding by 10% - 20% of aortic diameter of anchoring zone. Instant angiography revealed no endoleak in 12 patients, minor endoleak in 2 patients. Within the follow-up average 17.2 months, CT scans demonstrated the disappearances of penetrating atherosclerotic ulcer or exclusion of aortic pseudoaneurysm in all patients, and absorption of intramural hematoma in two patients. One patient died of rupture of aortic pseudoaneurysm after one month. CONCLUSION: Penetrating atherosclerotic ulcer can leads to intramural hematoma, dissection, aneurysmal dilatation, pseudoaneurysm, or aortic rupture. Therefore it should be treated once diagnosed. Endovascular stent-graft placement may be an effective treatment for penetrating atherosclerotic ulcer, especially in patients with poor condition.

[Morphological features of secundum atrial septal defect in adult and implications for transcatheter closure].

OBJECTIVE: To study the morphological features of secundum atrial septal defect (ASD) in adult and the implications for transcatheter closure. METHODS: Transcatheter closure using Amplatzer duct occluder was performed in 272 adult patients with ASD from September 1997 to December 2005. The morphological features were evaluated by transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE). The size, length and thickness of rims, occluder diameter, the complete closure rate, residual shunt rate and complications were compared in patients with deficient and/or thin rims (Group A, n = 135) and patients with well-developed rims (Group B, n = 137). RESULTS: The complete closure rate was 97.8% (132/135) in group A and 99.3% (136/137) in group B. There were 74 cases with deficient rims, 39 cases with thin rims and 22 cases with both deficient and thin rims in group A. Gender distribution, age, operation successful rate, residual shunt rate and complication rate were similar between the 2 groups. The defect diameters measured by TTE (18.9 +/- 5.5 mm vs. 16.5 +/- 4.8 mm, P < 0.01), TEE (22.7 +/- 5.0 mm vs. 20.0 +/- 5.5 mm, P < 0.01) and occluder diameters used (29.1 +/- 5.7 mm vs. 26.0 +/- 5.9 mm, P < 0.01) were significantly larger in groups A than that in group B. The systolic pulmonary artery pressure was also significantly higher in groups A than that in groups B (36.9 +/- 11.9 mm Hg vs. 32.6 +/- 9.1 mm Hg, P < 0.01). There are significant correlations between occluder diameters and defects measured by either TTE or TEE in both groups (group A, TTE: r = 0.709, TEE: r = 0.850; group B, TTE: r = 0.716, TEE: r = 0.915, P all < 0.01). CONCLUSIONS: Poor residual rims were found in around 50% of adult patients with ASD. Transcatheter closure of these defects could be successfully performed with larger occluders. The defect diameters measured by TTE and TEE, especially the latter, could guide the occluder selection.