Case Report: Using Medtronic AP360 mechanical prosthesis in mitral valve replacement for patients with mitral insufficiency after primum atrial septal defect repair to reduce left ventricular outflow tract obstruction risk

BackgroundAtrial septal defect is one of the most common congenital heart diseases in adults. Primum atrial septal defect (PASD) accounts for 4%–5% of congenital heart defects. Patients with PASD frequently suffer mitral insufficiency (MI), and thus, mitral valvuloplasty (MVP) or mitral valve replacement (MVR) is often required at the time of PASD repair. Unfortunately, recurrent unrepairable severe mitral regurgitation can develop in many patients undergoing PASD repair plus MVP in either short- or long-term after the repair surgery, requiring a re-do MVR. In those patients, the risk of left ventricular outflow tract obstruction (LVOTO) has increased.Case presentationWe present five such cases, ranging in age from 24 to 47 years, who had a PASD repair plus MVP or MVR for 14–40 years while suffering moderate to severe mitral regurgitation. Using Medtronic AP360 mechanical mitral prostheses, only one patient experienced mild LVOTO.ConclusionsThe use of Medtronic AP360 mechanical mitral prostheses to perform MVR in patients with MI who had a history of PASD repair can potentially reduce the risk of LVOTO. Long-term follow-up is required to further confirm this clinical benefit associated with AP360 implantation in patients with PASD

Identification of PDCD1 as a potential biomarker in acute rejection after kidney transplantation via comprehensive bioinformatic analysis

BackgroundAcute rejection is a determinant of prognosis following kidney transplantation. It is essential to search for novel noninvasive biomarkers for early diagnosis and prompt treatment.MethodsGene microarray data was downloaded from the Gene Expression Omnibus (GEO) expression profile database and the intersected differentially expressed genes (DEGs) was calculated. We conducted the DEGs with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Distribution of immune cell infiltration was calculated by CIBERSORT. A hub gene marker was identified by intersecting the rejection-related genes from WGCNA and a selected KEGG pathway—T cell receptor signaling pathway (hsa04660), and building a protein-protein interaction network using the STRING database and Cytoscape software. We performed flow-cytometry analysis to validate the hub gene.ResultsA total of 1450 integrated DEGs were obtained from five datasets (GSE1563, GSE174020, GSE98320, GSE36059, GSE25902). The GO, KEGG and immune infiltration analysis results showed that AR was mainly associated with T cell activation and various T-cell related pathways. Other immune cells, such as B cells, Macrophage and Dendritic cells were also associated with the progress. After utilizing the WGCNA and PPI network, PDCD1 was identified as the hub gene. The flow-cytometry analysis demonstrated that both in CD4+ and CD8+ T cells, PD1+CD57-, an exhausted T cell phenotype, were downregulated in the acute rejection whole blood samples.ConclusionsOur study illustrated that PDCD1 may be a candidate diagnostic biomarker for acute kidney transplant rejection via integrative bioinformatic analysis

NMR-based Metabolomic Analysis of Human Bladder Cancer

Bladder cancer (BC) is one of the most common cancers and has a high mortality rate. However, both metabolite variations and metabolic pathways related to the pathogenic process of BC remain to be addressed, such results might contribute to early detection of the disease. H-1 nuclear magnetic resonance (NMR)-based metabolomics was applied to identify differences of serum metabolic profiles among BC, calculi patients and healthy subjects. Serum metabolic profiles of BC patients are distinctly different from those of calculi and healthy subjects. Compared with those from healthy subjects, serum samples from BC patients show decreased levels of isoleucine/leucine, tyrosine, lactate, glycine, citrate, as well as increased levels of lipids and glucose. The results reveal disturbed metabolic pathways of aromatic amino acids, glycolysis and citrate cycle, as well as lipogenesis metabolism in BC patients. Our work will be of potential benefit to understanding the pathogenic process of BC and will offer valuable information for noninvasive diagnosis of the disease.National Natural Science Foundation of China [81100598, 91129713, 31170717]; Program of Shanghai Subject Chief Scientist [09XD1405100

Impact of prosthesis–patient mismatch on short-term outcomes after aortic valve replacement: a retrospective analysis in East China

Abstract Background Prosthesis–patient mismatch (PPM) may affect the clinical outcomes of patients undergoing aortic valve replacement (AVR). We aimed to determine the incidence of PPM, its effect on short-term mortality, and the factors contributing to PPM in China. Methods We retrospectively examined all consecutive patients with isolated or concomitant AVR at our hospital between January 1, 2013 and December 31, 2015. PPM was defined as an effective orifice area index (EOAi) of ≤ 0.85 cm2/m2. The baseline, echocardiographic, operative, and outcome data of all patients were collected from the national database. Results A total of 869 patients were included in the study. PPM was detected in 15.9% (138/869) of the patients. Four patients (0.5%) met the criteria for severe PPM. Patients with PPM were older and had a higher prevalence of diabetes, coronary heart disease, aortic stenosis (AS), and preoperative left ventricular dysfunction but a lower incidence of smoking history and aortic regurgitation. Logistic regression analysis showed that female gender (P < 0.001), AS (P = 0.014), higher body mass index (BMI) (P < 0.001), and bioprosthesis (P < 0.001) were independent predictors of PPM. We also found that PPM (P = 0.005) was associated with 30-day all-cause mortality, along with smoking history (P = 0.001) and low preoperative left ventricular ejection fraction (LVEF) (P = 0.004). Conclusions PPM is associated with high short-term mortality after AVR in China. Female gender, aortic stenosis, bioprosthesis, and high BMI are risk factors for the incidence of PPM

Comparison of the Radiation Shielding Properties of Wall Materials for the Manned Spacecraft for Future China Space Exploration Missions

International audienceThe radiation environment in space poses significant challenges to human health, and it is a major concern in long duration, manned space missions. Outside Earth’s protective magnetosphere, astronauts are exposed to higher levels of galactic cosmic rays (GCRs), whose physical characteristics are distinct from those of terrestrial sources of radiation, such as X-rays and gamma-rays. GCRs include high-energy heavy ions, many of which have ranges that exceed the depth of shielding and can be launched in realistic scenarios. Protecting the astronauts from these particles has been a key issue in manned space missions. Therefore, a need exists for reliable simulations of these harmful effects for risk assessment and shielding optimization in manned space missions. The aim of this work was to investigate shielding materials that can be used in deep space and planetary exploration. In this work, we used the Geant4 radiation transport code, originally developed by the International Geant4 Collaboration, and we compared the radiation shielding effectivenesses of polyethylene, aluminum, water, and carbon fiber targets hit by 1GeV/nucleon 56Fe (considered as a representative of high-energy GCR). In addition, the total absorbed doses at the water phantom behind these targets were calculated using the Geant4 simulation code. The calculated results were analyzed, compared, and discussed. The results show that polyethylene is the best space radiation shielding material for a given areal density, followed by water, carbon fiber, and then aluminum

Proteasome inhibitors enhance endothelial thrombomodulin expression via induction of Krüppel-like transcription factors

OBJECTIVE: Impairment of the thrombomodulin-protein C anticoagulant pathway has been implicated in pathological thrombosis associated with malignancy. Patients who receive proteasome inhibitors as part of their chemotherapeutic regimen appear to be at decreased risk for thromboembolic events. We investigated the effects of proteasome inhibitors on endothelial thrombomodulin expression and function. METHODS AND RESULTS: Proteasome inhibitors as a class markedly induced the expression of thrombomodulin and enhanced the protein C activating capacity of endothelial cells. Thrombomodulin upregulation was independent of NF-kappaB signaling, a principal target of proteasome inhibitors, but was instead a direct consequence of increased expression of the Krüppel-like transcription factors, KLF2 and KLF4. These effects were confirmed in vivo, where systemic administration of a proteasome inhibitor enhanced thrombomodulin expression that was paralleled by changes in the expression of KLF2 and KLF4. CONCLUSIONS: These findings identify a novel mechanism of action of proteasome inhibitors that may help to explain their clinically observed thromboprotective effect

Somatic FGFR3 Mutations Distinguish a Subgroup of Muscle-Invasive Bladder Cancers with Response to Neoadjuvant ChemotherapyResearch in Context

The administration of neoadjuvant chemotherapy (NAC) preceding radical cystectomy benefits overall survival for patients with muscle-invasive bladder cancer (MIBC). However, the relationship between the genetic profiling of MIBC and NAC response remains unclear. Here, a mutation panel of six cancer-associated genes (TSC1, FGFR3, TERT, TP53, PIK3CA and ERBB2) and an immunohistochemistry (IHC) panel containing eight bladder cancer (BC) biomarkers (EGFR, RRM1, PD-L1, BRCA1, TUBB3, ERCC, ERCC1, aberrantly glycosylated integrin α3β1 (AG) and CK5/6) were developed. BC samples from patients who showed a pathologic response (n = 39) and non-response (n = 13) were applied to the panel analysis. ERBB2, FGFR3 and PIK3CA exclusively altered in the responders group (19/39, 48.7%), in which FGFR3 mutations were significantly enriched in patients with a response in the cohort (14/39, 35.9%; P = 0.01). Additionally, strong expression of ERCC1 was associated with a pathologic response (P = 0.01). However, positive lymph node metastasis (P < 0.01) and lymph-vascular invasion (LVI) (P = 0.03) were correlated with a non-response. Overall, the data show that FGFR3 mutations and elevated expression of ERCC1 in MIBCs are potential predictive biomarkers of the response to NAC. Keywords: Bladder cancer, Neoadjuvant chemotherapy, FGFR3, ERCC