Effectiveness and feasibility of transcatheter aortic valve replacement in treating combined aortic and mitral regurgitation: a retrospective observational study.

Background: Transcatheter aortic valve replacement (TAVR) is emerging as a less invasive procedure for aortic valve replacement. However, its effectiveness and feasibility in treating combined valvular disease remain controversial. In this study, we explored the clinical effectiveness and safety of TAVR in the treatment of combined aortic and mitral regurgitation. Methods: The basic clinical characteristics and 1-month follow-up of 11 patients with combined aortic and mitral regurgitation who were treated with TAVR at center of structural heart disease, Zhongnan Hospital of Wuhan University from December 2021 to November 2022 were retrospectively analyzed. Echocardiographic parameters of aortic and mitral valve, complications, and all-cause mortality were compared pre- and post-TAVR. Results: Retrievable self-expanding valve protheses were used in all patients, and the protheses were implanted via the transfemoral route in 8 patients and via the transapical route in 3 patients. There were 9 male and 2 female patients with an average age of 74.7±2.7 years. The mean Society of Thoracic Surgeons score was 8.5±1.2. Among the patients, 1 required retroperitoneal sarcoma semi-elective surgery, and 3 of the 5 patients with atrial fibrillation had their rhythm converted to sinus rhythm after operation. No perioperative deaths were recorded. Two patients underwent permanent pacemaker implantations due to high-grade atrioventricular blocks after TAVR. Moderate/severe mitral regurgitation (MR) were mostly secondary to aortic regurgitation (AR) as no rupture of the subvalvular tendon cords or rheumatic changes being recognized during echocardiography before operation. The mean left ventricular end-diastolic diameter (65.5±10.7 vs. 58.6±8.8 mm, P<0.001) and mitral annular diameter (36.7±5.4 vs. 31.5±2.8 mm, P<0.001) was significantly reduced after operation. MR was improved as the ratio of the regurgitant jet area to the left atrial area decreased significantly after operation (24.7%±11.5% vs. 42.4%±6.8% before operation, P<0.001). During the 1-month follow-up, the mean left ventricular ejection fraction was significantly improved (50.0%±9.4% vs. 44.6%±9.3% at admission, P=0.022). Conclusions: TAVR is effective and feasible for high-risk patients with combined aortic and mitral regurgitation.

Microplastics removal and characteristics of a typical multi-combination and multi-stage constructed wetlands wastewater treatment plant in Changsha, China.

Wastewater treatment plants (WWTPs) are an important source of microplastics (MPs) entering the aquatic environment. As environmental awareness increases, WWTPs are gradually using constructed wetlands (CWs) in the depth treatment stage. There were few studies related to MPs removal efficiency of CWs, especially in multi-stage and multi-combinations CWs. Therefore, we studied MPs characteristics and removal in a typical CWs WWTP in Changsha, comparing the MPs removal efficiencies of different processes in a WWTP, focusing on the MPs abundance variation in different stages CWs. Result showed that the MPs removal efficiency of Phase Ⅰ was 87.72% and that of Phase II was 80.65%. Approximate estimates showed that the daily discharge of MPs reached 7.20 * 108 items. The MPs removal efficiency of vertical flow CWs was 25.71%. The MPs removal efficiencies of secondary and tertiary horizontal subsurface flow CWs (HSSFCWs) were 32.00% and 21.43%. The MPs removal efficiencies of secondary and tertiary surface flow CWs were 23.53% and 12.50%. The MPs removal efficiencies of three bio-ponds were -23.08%, -12.90%, and -27.27%. Combined system of bio-pond + CWs reduced the MPs removal efficiency. The most dominant shape of MPs in wastewater was fibers. The most common MPs were polyethylene and polystyrene. The primary treatment in the Changsha WWTP had the highest MPs removal efficiency. Results of this investigation showed the multi-combination and multi-stage CWs WWTP can remove most of MPs in influent, which greatly reduced the amount of MPs discharged into the aquatic environment through WWTP and provided data for analyzing the distribution of MPs in the aquatic environment.

Iodine-Rich Polymersomes Enable Versatile SPECT/CT Imaging and Potent Radioisotope Therapy for Tumor in Vivo.

Emerging tumor treatment demands high sensitivity and high-spatial resolution diagnosis in combination with targeted therapy. Here, we report that iodine-rich polymersomes (I-PS) enable versatile single-photon emission computed tomography (SPECT)/computed tomography (CT) dual-modal imaging and potent radioisotope therapy for breast cancer in vivo. Interestingly, I-PS could be easily and stably labeled with radioiodine, 125I and 131I. Dynamic light scattering and transmission electron microscopy showed that 125I-PS had a size of 106 nm and vesicular morphology, similar to those of the parent I-PS. Methyl thiazolyl tetrazolium assays displayed that I-PS and 125I-PS were noncytotoxic, whereas 131I-PS caused significant death of 4T1 cells at 5 mg PS/mL with a radioactivity of 12 µCi. Pharmacokinetic and biodistribution studies showed that 125I-PS has a prolonged circulation and distributes mainly in tumor and the reticuloendothelial system. The intravenous injection of 125I-PS to 4T1 murine breast tumor-bearing mice allowed simultaneous high sensitivity and high-spatial resolution imaging of tumor by SPECT and CT, respectively. The therapeutic studies revealed that 131I-PS could effectively retard the growth of 4T1 breast tumor and significantly prolong mice survival time. The hematoxylin and eosin staining assay proved that 131I-PS induced tumor cell death. I-PS emerges as a robust and versatile platform for dual-modal imaging and targeted radioisotope therapy.

Boosting RNAi therapy for orthotopic glioblastoma with nontoxic brain-targeting chimaeric polymersomes.

Glioblastoma with intracranial infiltrative growth remains an incurable disease mainly owing to existence of blood brain barrier (BBB) and off-target drug toxicity. RNA interference (RNAi) with a high specificity and low toxicity emerges as a new treatment modality for glioblastoma. The clinical application of RNAi technology is, however, hampered by the absence of safe and brain-targeting transfection agents. Here, we report on angiopep-2 peptide-decorated chimaeric polymersomes (ANG-CP) as a nontoxic and brain-targeting non-viral vector to boost the RNAi therapy for human glioblastoma in vivo. ANG-CP shows excellent packaging and protection of anti-PLK1 siRNA (siPLK1) in its lumen while quickly releasing payloads in a cytoplasmic reductive environment. Notably, in vitro experiments demonstrate that ANG-CP can effectively permeate the bEnd.3 monolayer, transport siRNA into the cytosol of U-87 MG glioblastoma cells via the LRP-1-mediated pathway, and significantly silence PLK1 mRNA and corresponding oncoprotein in U-87 MG cells. ANG-CP greatly prolongs the siPLK1 circulation time and enhances its accumulation in glioblastoma. RNAi with siPLK1 induces a strong anti-glioblastoma effect and significantly improves the survival time of glioblastoma carrying mice.

Characterization of a novel hemolytic activity of human IgG fractions arising from diversity in protein and oligosaccharide components.

Human IgG is a well-established multifunctional antigen specific immunoglobulin molecule of the adaptive immune system. However, an antigen nonspecific immunological function of human IgG has never been reported. In this study, human IgG was isolated using ammonium sulfate fractional precipitation and diethylaminoethanol (DEAE) cellulose 52 ion exchange chromatography, from which h-IgG and hs-IgG fractions were purified on the basis of their differential binding to rabbit anti-shrimp hemocyanin antibody (h) and rabbit anti-shrimp hemocyanin's small subunit antibody (hs), respectively. We found that h-IgG had a higher hemolytic activity than hs-IgG against erythrocytes from humans, rabbits, mice and chickens, whereas the control IgG showed negligible activity. h-IgG could interact directly with erythrocyte membranes, and this interaction was suppressed by high molecular weight osmoprotectants, showing that it may follow a colloid-osmotic mechanism. In comparative proteomics and glycomics studies, h-IgG and hs-IgG yielded 20 and 5 significantly altered protein spots, respectively, on a 2-D gel. The mean carbohydrate content of h-IgG and hs-IgG was approximately 3.6- and 2-fold higher than that of IgG, respectively, and the α-d-mannose/α-d-glucose content was in the order of h-IgG>hs-IgG>IgG. In this study, a novel antigen nonspecific immune property of human IgG was investigated, and the diversity in the protein constituents and glycosylation levels may have functional signficance.