Follistatin-like protein 1 attenuates doxorubicin-induced cardiomyopathy by inhibiting MsrB2-mediated mitophagy.

Doxorubicin (DOX) is a potent chemotherapeutic drug; however, its clinical use is limited due to its cardiotoxicity. Mitochondrial dysfunction plays a vital role in the pathogenesis of DOX-induced cardiomyopathy. Follistatin-like protein 1 (FSTL1) is a potent cardiokine that protects the heart from diverse cardiac diseases, such as myocardial infarction, cardiac ischemia/reperfusion injury, and heart failure. However, its role in DOX-induced cardiomyopathy is unclear. Therefore, the present study investigated whether administering recombinant FSTL1 could mitigate DOX-induced cardiomyopathy and clarified the underlying molecular mechanisms. FSTL1 treatment attenuated DOX-induced cardiac dysfunction, cardiac fibrosis, and cellular apoptosis by inhibiting excess mitochondrial matrix protein methionine sulfoxide reductase B2 (MsrB2)-mediated mitophagy. Furthermore, FSTL1 administration reduced the expression of apoptotic proteins, including MsrB2, Bax, caspase 3, mitochondrial Parkin, and LC3-II, increased myocardial ATP content, and decreased cardiac malondialdehyde levels, thus protecting mitochondrial function against DOX-induced cardiac injury. Furthermore, FSTL1 treatment protected the contractile properties of adult cardiomyocytes against DOX-induced injury in vitro. Furthermore, carbonyl cyanide m-chlorophenylhydrazone, a mitophagy inducer, impaired the protective effects of FSTL1 in DOX-treated H9c2 cardiomyocytes. In conclusion, these results show that FSTL1 is a novel therapeutic agent against DOX-induced cardiotoxicity that improves mitochondrial function and decreases mitophagy.

FPR1: A critical gatekeeper of the heart and brain.

G protein-coupled receptors (GPCRs) are currently the most widely focused drug targets in the clinic, exerting their biological functions by binding to chemicals and activating a series of intracellular signaling pathways. Formyl-peptide receptor 1 (FPR1) has a typical seven-transmembrane structure of GPCRs and can be stimulated by a large number of endogenous or exogenous ligands with different chemical properties, the first of which was identified as formyl-methionine-leucyl-phenylalanine (fMLF). Through receptor-ligand interactions, FPR1 is involved in inflammatory response, immune cell recruitment, and cellular signaling regulation in key cell types, including neutrophils, neural stem cells (NSCs), and microglia. This review outlines the critical roles of FPR1 in a variety of heart and brain diseases, including myocardial infarction (MI), ischemia/reperfusion (I/R) injury, neurodegenerative diseases, and neurological tumors, with particular emphasis on the milestones of FPR1 agonists and antagonists. Therefore, an in-depth study of FPR1 contributes to the research of innovative biomarkers, therapeutic targets for heart and brain diseases, and clinical applications.

Isopropyl 3-(3,4-dihydroxyphenyl) 2-hydroxypropanoate protects septic myocardial injury via regulating GAS6/Axl-AMPK signaling pathway.

In a previous study, we used metabolomic techniques to identify a new metabolite of Danshen Dripping Pills called isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP), which has potential as a drug candidate for cardiovascular diseases. This study aimed to explore the protective effects of IDHP against septic myocardial injury, as well as its molecular mechanism. Wild type or GAS6 knockout mice injured by cecal ligation and puncture (CLP) were used to observe the effect of IDHP. Here, we found that a specific concentration of IDHP (60 mg/kg) significantly increased the survival rate of septic mice to about 75 % at 72 h post CLP, and showed improvements in sepsis score, blood biochemistry parameters, cardiac function, and myocardial tissue damage. Furthermore, IDHP inhibited myocardial oxidative stress, inflammatory response, apoptosis, and mitochondrial dysfunction. Molecularly, we discovered that IDHP treatment reversed the CLP-induced downregulation of GAS6, Axl, and p-AMPK/AMPK expression. In addition, GAS6 knockout reversed the positive effect of IDHP in septic mice, indicated by more severe myocardial tissue damage, oxidative stress, inflammatory response, and mitochondrial dysfunction. GAS6 knockout also resulted in decreased levels of GAS6, Axl, and p-AMPK/AMPK. Taken together, our study provides evidence that IDHP has significant cardioprotective effects against sepsis by regulating the GAS6/Axl-AMPK signaling pathway. This finding has important therapeutic potential for treating sepsis.

Irisin improves diabetic cardiomyopathy-induced cardiac remodeling by regulating GSDMD-mediated pyroptosis through MITOL/STING signaling.

Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM). However, the mechanisms underlying DCM-induced cardiac injury remain unclear. Recently, the role of cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) signaling and pyroptosis in DCM has been investigated. Based on our previous results, this study was designed to examine the impact of irisin, mitochondrial ubiquitin ligase (MITOL/MARCH5), and cGAS/STING signaling in DCM-induced cardiac dysfunction and the effect of gasdermin D (GSDMD)-dependent pyroptosis. High-fat diet-induced mice and H9c2 cells were used for cardiac geometry and function or pyroptosis-related biomarker assessment at the end of the experiments. Here, we show that DCM impairs cardiac function by increasing cardiac fibrosis and GSDMD-dependent pyroptosis, including the activation of MITOL and cGAS/STING signaling. Our results confirmed that the protective role of irisin and MITOL was partially offset by the activation of cGAS/STING signaling. We also demonstrated that GSDMD-dependent pyroptosis plays a pivotal role in the pathological process of DCM pathogenesis. Our results indicate that irisin treatment protects against DCM injury, mitochondrial homeostasis, and pyroptosis through MITOL upregulation.

Pentraxin 3: A promising therapeutic target for cardiovascular diseases.

Cardiovascular disease (CVD) is the primary global cause of death, and inflammation is a crucial factor in the development of CVDs. The acute phase inflammatory protein pentraxin 3 (PTX3) is a biomarker reflecting the immune response. Recent research indicates that PTX3 plays a vital role in CVDs and has been investigated as a possible biomarker for CVD in clinical trials. PTX3 is implicated in the progression of CVDs through mechanisms such as exacerbating vascular endothelial dysfunction, affecting angiogenesis, and regulating inflammation and oxidative stress. This review summarized the structure and function of PTX3, focusing on its multifaceted effects on CVDs, such as atherosclerosis, myocardial infarction, and hypertension. This may help in explaining the varying PTX3 functions and usage, as well as in utilizing target organs to manage diseases. Moreover, elucidating the opposite role of PTX3 in the cardiovascular system will demonstrate the therapeutic and predictive potential in human diseases.

Exploring the role of ITGB6: fibrosis, cancer, and other diseases.

Integrin ß6 (ITGB6), a member of the integrin family of proteins, is only present in epithelial tissues and frequently associates with integrin subunit αv to form transmembrane heterodimers named integrin αvß6. Importantly, ITGB6 determines αvß6 expression and availability. In addition to being engaged in organ fibrosis, ITGB6 is also directly linked to the emergence of cancer, periodontitis, and several potential genetic diseases. Therefore, it is of great significance to study the molecular-biological mechanism of ITGB6, which could provide novel insights for future clinical diagnosis and therapy. This review introduces the structure, distribution, and biological function of ITGB6. This review also expounds on ITGB6-related diseases, detailing the known biological effects of ITGB6.

Evaluation of inhalation toxicology after a 90-day xylitol aerosol exposure in Sprague-Dawley rats.

Xylitol is a hygroscopic compound known to protect nasal cavity against bacteria. It has also been developed into nasal spray and evaluated as a potential candidate drug for respiratory diseases. Consequently, it is necessary to study its inhalation toxicity. Based on our previous study on its subacute inhalation toxicity, this study aimed to investigate the safety of xylitol inhalation for long-term use. According to the OECD Test Guideline 413, Sprague-Dawley rats were randomly divided into six groups and exposed with different concentrations of xylitol aerosol or air. After exposure for 90-day, the recovery groups were continued to observe for a recovery period of 28-day. No significant changes in body weight were observed between sham and xylitol groups. Several significant differences in hematological, clinical chemistry, bronchoalveolar lavage fluid were observed, which either had no dose-effect relationship for both male and female rats or were restored during the recovery period. Finally, except for high dose group of xylitol, two rats showed a small amount of inflammatory exudate in alveolar and bronchial cavities, which was restored in the recovery period. The rest of rats showed no obvious difference. For the recovery groups, no significant difference was observed between these two groups. In conclusion, the no observable adverse effect level (NOAEL) of xylitol in our subchronic inhalation toxicological experiments was 2.9 mg/L, which indicated that xylitol for rats' long-time inhalation is tolerant and safe.

CD4+FoxP3+CD73+ regulatory T cell promotes cardiac healing post-myocardial infarction.

Rationale: Despite recent studies indicating a crucial role of ecto-5'-nucleotidase (CD73) on T cells in cardiac injury after ischemia/reperfusion, the involvement of CD73+ regulatory T cells (Tregs) in cardiac repair post-myocardial infarction (MI) remains unclear. We sought to investigate the contribution of CD73 on Tregs to the resolution of cardiac inflammation and remodeling after MI. Methods: Cardiac function, tissue injury, Tregs percentage in injured hearts, and purinergic signaling changes in cardiac FoxP3+ Tregs were analyzed after permanent descending coronary artery ligation. CD73 knockout Tregs were used to determine the function of CD73 on Tregs. Peripheral blood mononuclear cells (PBMCs) from acute myocardial infarction (AMI) patients and matched non-MI subjects were assessed via flow cytometry. Results: Cardiac Tregs exhibited distinction of purinergic signaling post MI with dramatically high level of CD73 compared to the sham Tregs. CD73 deficiency decreased the tissue tropism, and impaired the immunosuppressive and protective function of Tregs in cardiac healing. Administration of low-dose of IL-2/anti-IL-2 complex resulted in FoxP3+CD73+Tregs expansion in the heart and contributed to the recovery of cardiac function. CD73 derived from FoxP3+Tregs could bind to FoxP3- effector T-cells and inhibit the production of multiple inflammatory cytokines. In AMI patients, CD73 expressions on both CD4+ cells and FoxP3+Tregs decreased in PBMCs. Moreover, CD73 expressions on CD4+ T cells were negatively correlated with the levels of NT pro-BNP and myocardial zymogram in serum. Conclusions: Our findings indicated the importance of FoxP3+CD73+Tregs in inflammation resolution and cardiac healing post-MI.

Toxicity evaluation in rats following 28 days of inhalation exposure to xylitol aerosol.

Xylitol has reported to decrease gingival inflammation and nasopharyngeal pneumonia, which indicated that xylitol may have potential application in respiratory diseases. Although some studies have reported the inhalation toxicity of xylitol, however, the longest period tested was only for 14 days. The inhalation toxicity of xylitol is insufficient. This work investigated the potential subacute toxicity of xylitol according to the OECD TG 412. Rats were randomly divided into a control group and different dosage groups (2 g/m3, 3 g/m3, 5 g/m3), and exposed for 6 hours/day, 5 days/week for 28 days. At the end of the exposure or recovery period, clinical signs, mortality, body weight, food consumption, hematology, blood biochemistry, gross pathology, organ weight, and histopathology were examined. Compared with the control group, rats of both sexes in the exposure groups exhibited no significant changes in body weight, organ mass, and food uptake. After the xylitol exposure, aspartate aminotransferase activity in the xylitol group (3 g/m3) was significantly higher than that in the control group, while other blood indicators and pathological changes of liver and the analysis of the recovery group showed no changes, suggesting that xylitol exerted no observable toxic effect on the liver. Finally, other observations including the histopathology of target organs and hematology also showed no alterations. These results indicated that xylitol had no significant inhalation toxicity at doses up to 5 g/m3. These subacute inhalation toxicity results of xylitol showed that its no-observed-adverse-effect concentration (NOAEC) in rats was determined to 5 g/m3.

Effect of Eccentric Calcification of an Aortic Valve on the Implant Depth of a Venus-A Prosthesis During Transcatheter Aortic Valve Replacement: A Retrospective Study.

OBJECT: Our goal was to assess the implant depth of a Venus-A prosthesis during transcatheter aortic valve replacement (TAVR) when the areas of eccentric calcification were distributed in different sections of the aortic valve. METHODS: A total of 53 patients with eccentric calcification of the aortic valve who underwent TAVR with a Venus-A prosthesis from January 2018 to November 2019 were retrospectively analyzed. The patients were divided into three groups (A, B, and C) according to the location of the eccentric calcification, which was determined by preprocedural computerized tomography angiography (CTA) images. The prosthesis release process and position were evaluated by contrast aortography during TAVR, and the differences in valve implant depths were compared among the three groups. The effects of different aortic root structures and procedural strategies on prosthesis implant depth were analyzed. RESULTS: Eleven patients had eccentric calcification in region A; 19 patients, in region B; and 23 patients, in region C. The patients with eccentric calcification in region B had a higher risk of prosthesis migration (10.5% upward and 21.1% downward), and the position of the prosthesis after TAVR in group B was the deepest among the three groups. When eccentric calcification was located in region A or C, the prosthesis was released at the standard position with more stability, and the location of the prosthesis was less deep after TAVR (region A: 4.12 ± 3.4 mm; region B: 10.2 ± 5.3 mm; region C: 8.4 ± 4.0 mm; region A vs. region B, P = 0.0004; region C vs. region B; and P = 0.0360). In addition, the left ventricular outflow tract (LVOT) (P = 0.0213) and aortic root angulation (P = 0.0263) also had a significant effect on implant depth in the aortic root structure of the patients. The prosthesis size was 28.3 ± 2.4 in the deep implant group and 26.4 ± 2.0 in the appropriate implant group (P = 0.0068). CONCLUSION: The implant depth of the Venus-A prosthesis is closely related to the distribution of eccentric calcification in the aortic valve during TAVR. Surgeons should adjust the surgical strategy according to aortic root morphology to prevent prosthesis migration.

Application of three-dimensional transesophageal echocardiography in preoperative evaluation of transcatheter aortic valve replacement.

BACKGROUND: Our goal was to determine the accuracy of 3-dimensional transesophageal echocardiography (3D-TEE) compared with that of computed tomography (CT) in the preoperative evaluation for transcatheter aortic valve replacement (TAVR) when the errors caused by inconsistent software and method have been eliminated and the representativeness of the sample has been improved. We also investigated the influence of aortic root calcification on the accuracy of 3D-TEE in aortic annulus evaluations. METHODS: Part I: 45 of 233 patients who underwent TAVR in the department of cardiovascular surgery at the Xijing hospital from January 2016 to August 2019 were studied retrospectively. Materialise Mimics software and the multiplanar reconstruction method were used for evaluation, based on 3D-TEE and CT. The annulus area-derived diameter, the annulus perimeter-derived diameter (Dp), the annulus mean diameter, the left ventricular outflow tract Dp diameter, the sinotubular junction (STJ) diameter-Dp, and the aortic sinus diameter were compared and analyzed. Part II: 31 of 233 patients whose 3D-TEE and CT data were well preserved and in the required format were included. HU450 and HU850 were used as indicators to measure the severity of calcification. The Spearman rank correlation and Linear regression were used to analyze the correlation between aortic root calcification and the accuracy of 3D-TEE in aortic annulus measurement. RESULTS: The measurement results based on 3D-TEE were significantly lower than those obtained using CT (P < 0.05), except for the STJ diameter-Dp in diastole (P = 0.11). The correlation coefficient of the two groups was 0.699-0.954 (P < 0.01), which also indicated a significant correlation between the two groups. A Bland-Altman plot showed that the ordinate values were mostly within the 95% consistency limit; the consistency of the two groups was good. By establishing the linear regression equation, the two groups can be inferred from each other. The Spearman rank correlation analysis and the Linear regression analysis showed that the influence of aortic calcification on the accuracy of the 3D-TEE annulus evaluation was limited. CONCLUSIONS: Although an evaluation based on 3D-TEE underestimated the results, we can deduce CT results from 3D-TEE because the two methods exhibit considerable correlation and consistency. TRIAL REGISTRATION: Name: Surgery and Transcatheter Intervention for Structural Heart Diseases. Number: NCT02917980. URL: https://clinicaltrials.gov/ct2/results?term=NCT02917980 .

Three-dimensional printing for heart diseases: clinical application review.

Heart diseases remain the top threat to human health, and the treatment of heart diseases changes with each passing day. Convincing evidence shows that three-dimensional (3D) printing allows for a more precise understanding of the complex anatomy associated with various heart diseases. In addition, 3D-printed models of cardiac diseases may serve as effective educational tools and for hands-on simulation of surgical interventions. We introduce examples of the clinical applications of different types of 3D printing based on specific cases and clinical application scenarios of 3D printing in treating heart diseases. We also discuss the limitations and clinically unmet needs of 3D printing in this context.

Transcatheter Closure of Mitral Paravalvular Leak via Multiple Approaches.

OBJECTIVES: The purpose of this study was to review the experiences with transcatheter closure of mitral PVL after surgical valve replacement. BACKGROUND: Transcatheter closure of paravalvular leak (PVL) is an intricate alternative to surgical closure. But it represents one of the most intricate procedures in the field of structural heart interventions, especially for patients with mitral PVL. METHODS: From January 2015 through January 2019, 35 patients with mitral PVL after valve replacement underwent transcatheter closure. We reviewed the catheter techniques, perioperative characteristics, and prognosis. The median follow-up was 26 (3-48) months. RESULTS: Acute procedural success was achieved in 33/35 (94.3%) patients. Twenty-five patients had single mitral prosthetic valve replacements; 10 had combined aortic and mitral prosthetic valve replacements previously; 28 had mechanical valves; and 7 had bioprosthetic valves. All percutaneous procedures were performed with local anesthesia except for seven transapical cases with general anesthesia. Multiple approaches were used: transfemoral, transapical, and transseptal via an arteriovenous loop. Multiple devices were deployed. There were no hospital deaths. The procedural time was 67-300 (124 ± 62) minutes. Fluoroscopic time was 17-50 (23.6 ± 12.1) minutes. The hospital stay was 5-17 (8.3 ± 3.2) days. Complications included recurrent hemolysis, residual regurgitation, acute renal insufficiency, and anemia. Twenty-seven (77.1%) patients improved by ≥1 New York Heart Association functional class at the 1-year follow-up. CONCLUSIONS: Transcatheter mitral PVL closure requires complex catheter techniques. However, this minimally invasive treatment could provide reliable outcomes and shorter hospital stays in selected patients. This trial is registered with NCT02917980.

Transcatheter mitral valve implantation using a novel system: preclinical results.

BACKGROUND: This preclinical study in sheep sought to demonstrate the initial safety and feasibility of a novel transcatheter mitral valve system (Mi-thos valve) composed of a self-expanding frame and a bovine pericardial tissue bioprosthesis. METHODS: The valve was implanted in 26 sheep using a transapical approach for short- and long-term evaluation. The technical feasibility, safety, durability, and valve function were evaluated during and 6 months after the procedure using intracardiac and transthoracic echocardiography, multisliced computed tomography, histological analysis, and electron microscopy. RESULTS: The success rate of valve implantation was 100%, and the immediate survival rate after surgery was 84%. Five animals died within 90 min after the development of the prosthetic valve due to an acute left ventricular outflow tract obstruction (n = 2) and sudden intraoperative ventricular fibrillation (n = 3). Twelve animals died within 1 month due to acute left heart dysfunction. Mild (n = 5) and moderate (n = 2) paravalvular leakage occurred in seven animals, and two moderate PVL animals died of chronic heart failure within three months. Multimodality imaging studies of the remaining seven animals showed excellent function and alignment of the valves, with no coronary artery obstruction, no left ventricular outflow tract obstruction, no severe transvalvular gradients and no paravalvular leakage. Macroscopic evaluation demonstrated stable, secure positioning of the valve, with full endothelialization of the valve leaflets without injury to the ventricular or atrial walls. Histological and electron microscopic examinations at six months showed no obvious macro- or microcalcification in the leaflets. CONCLUSIONS: Preclinical studies indicate that transcatheter implantation of the Mi-thos valve is technically safe and feasible. The durability, functionality, and lack of leaflet calcification were all verified in animal experiments. The information from these preclinical studies will be applied to patient selection criteria and the first-in-human studies.

Exosomes Derived from Mesenchymal Stem Cells Protect the Myocardium Against Ischemia/Reperfusion Injury Through Inhibiting Pyroptosis.

OBJECTIVE: Mesenchymal stem cells (MSCs) show unique advantages in cardiomyocyte repairment. Exosomes derived from MSCs can enhance the viability of myocardial cells after ischemia/reperfusion (I/R) injury and regulate inflammation response. The study was designed to ascertain whether MSCs-exo protect the myocardium against I/R injury through inhibiting pyroptosis, and the underlying mechanisms. METHODS AND RESULTS: Experiments were carried out in H/R and I/R model. Cell viability was inhibited and NLRP3 and caspase1 protein levels were upregulated in H/R model. However, MSCs could inhibit cell apoptosis and pyroptosis in H/R model. Moreover, we used MSCs-exo to treated H/R model, and flow cytometric analysis results showed the inhibition function of MSCs-exo on cell apoptosis, and Western blot data suggested that NLRP3 and Caspase-1 expressions were downregulated in H/R model. Furthermore, exosomal miR-320b targeted NLRP3 protein, and MSCs-exo OE could inhibit NLRP3 expression and pyroptosis in H/R. In addition, the inhibition function of MSCs-exo on pyroptosis also was found in I/R model, and HE and Tunel staining also got similar results. CONCLUSION: Exosomes derived from mesenchymal stem cells could protect the myocardium against ischemia/reperfusion injury through inhibiting pyroptosis.

Irisin attenuates myocardial ischemia/reperfusion-induced cardiac dysfunction by regulating ER-mitochondria interaction through a mitochondrial ubiquitin ligase-dependent mechanism.

BACKGROUND: Myocardial ischemia/reperfusion (MI/R) injury imposes devastating cardiovascular sequelae in particular cardiac dysfunction as a result of restored blood flow. However, the mechanism behind MI/R injury remains elusive. Mitochondrial ubiquitin ligase (MITOL/MARCH5) is localized at the mitochondria-ER contact site and may be activated in response to a variety of pathophysiological processes, such as apoptosis, mitochondrial injury, ER stress, hypoxia, and reactive oxygen species (ROS) generation. Irisin as a cleaved product of fibronectin type III domain-containing protein 5 (FNDC5) displays cardioprotection in diverse cardiac diseases. METHODS: This study was designed to examine the role of irisin and MITOL in MI/R injury. Male C57BL/6J mice (8-10-week-old) were administered adenovirus MITOL shRNA through intracardiac injection followed by MI/R surgery through ligation and release the slipknot of cardiac left anterior descending coronary artery. RESULTS: Our results showed that irisin improved myocardial function in the face of MI/R injury as evidenced by reduced myocardial infarct size, apoptotic rate, serum lactate dehydrogenase (LDH), ROS generation, and malondialdehyde (MDA) levels as well as lessened ER stress injury. Moreover, our results indicated that protective role of irisin was mediated by upregulation of MITOL. Irisin also protected H9c2 cells against simulated I/R through negating ER stress, apoptosis, ROS and MDA levels, as well as facilitating superoxide dismutase (SOD) by way of elevated MITOL expression. CONCLUSIONS: To this end, our data favored that irisin pretreatment protects against MI/R injury, ER stress, ROS production, and mitochondrial homeostasis through upregulation of MITOL. These findings depicted the therapeutic potential of irisin and MITOL in the management of MI/R injury in patients with ST-segment elevation.

Genome-wide analysis revealed the virulence attenuation mechanism of the fish-derived oral attenuated Streptococcus iniae vaccine strain YM011.

Streptococcus iniae has become one the most serious aquatic pathogens causing invasive diseases in farmed marine and freshwater fish worldwide, and orally attenuated vaccine is still the best option in protecting these invasive diseases. In this study, the safety, stability, immunogenicity of the S. iniae attenuated strain YM011 were evaluated, and comprehensively analyzed its virulence weakening mechanism at whole genome level. The results shown that attenuated S. iniae strain YM011 completely lost its pathogenicity to tilapia and had good immunogenicity with relative percent survival being 93.25% at 15 days and 90.31% at 30 days via IP injection, respectively, and 76.81% at 15 days and 56.69% at 30 days via oral gavage, respectively. Back-passage safety assay indicated that YM011 did not cause diseases or death in tilapia after 100 generations of serial passaging. Comparative genome-wide sequencing shown that YM011 had a 0.4 M large inversion fragment compared with its parental strain virulent strain GX005, which encoded 372 genes including drug resistance genes pbp2A and tet, as well as known virulence factors including hemolysin transport system gene, recA, and mutator family transposase. The attenuated S. iniae strain YM011 is an ideal attenuated oral vaccine candidate with good immunogenicity, safety and stability. Abnormal expression of important drug resistance genes as well as known virulence factors due to inversion of a 0.4 M large fragment is the leading mechanism underlying its attenuated virulence.

Prognosis of Transcatheter Closure Compared with Surgical Repair of Paravalvular Leak after Prosthetic Valve Replacement: A Retrospective Comparison.

OBJECTIVE: Paravalvular leak (PVL) after valve replacement remains clinically challenging. Percutaneous closure is an effective therapy for patients with PVLs because reoperation is associated with high rates of morbidity and mortality. The purpose of this study was to retrospectively compare the clinical outcome of transcatheter closure and surgical repair in patients with a PVL. METHODS: From January 2000 to May 2016, 131 patients with PVL were treated at three major medical centers in China. Perioperative characteristics and outcomes of the procedure were reviewed. RESULTS: Sixty-eight (51.9%) patients with PVLs were treated with percutaneous transcatheter closure (group I). The procedure was successful in 67 (98%) with no hospital deaths. Sixty-three (48.1%) patients with PVLs had a reoperation (group II). Five of the surgical patients had a third open-heart operation for residual regurgitation, and one underwent successful percutaneous closure. Six patients died in the hospital postoperatively. All patients in group II but only 11 in group I needed perioperative blood transfusions. The procedural time and hospital stay after the procedure were significantly shorter in group I than in group II. At the 1-year follow-up, cardiac function improved by ≥ 1 New York Heart Association functional class in 55 (82%) patients in group I and in 39 (68%) patients in group II. CONCLUSIONS: Transcatheter closure was shown to be a safe, effective therapeutic option in patients with PVL. It was associated with a lower hospital mortality rate, shorter procedural time, and fewer blood transfusions than surgical treatment in selected patients.