Performance characterization and biocompatibility assessment of silicone polyurethanes for polymer heart valve applications.

Silicone polyurethanes have gained widespread application in the biomedical field due to their excellent biocompatibility. This study comprehensively investigates four silicone polyurethane materials suitable for polymer heart valves, each exhibiting distinct chemical compositions and structural characteristics, leading to significant differences, particularly in mechanical performance and biocompatibility. Surface analysis reveals an elevated surface silicon element content in all materials compared to the bulk, indicating a migration of silicon elements towards the surface, providing a structural basis for enhancing biological stability and biocompatibility. However, higher silicon content leads to a decrease in mechanical performance, potentially resulting in mechanical failure and rupture in artificial heart valves. Concerning biocompatibility, an increase in silicone content diminishes the material's adsorption capability for cells and proteins, consequently improving its biocompatibility and biological stability. In summary, while high silicone content leads to a reduction in mechanical performance, the formation of a "silicon protective layer" on the material surface mitigates cell and protein adsorption, thereby enhancing biocompatibility and biological stability. Through comprehensive testing of the four silicone polyurethane materials, this study aims to provide insightful perspectives and methods for selecting materials suitable for polymer heart valves. Additionally, the thorough performance exploration of these materials serves as a crucial reference for the performance assessment and biocompatibility research of polymeric artificial heart valve materials.

Optimal treatment of tannic acid for the anti-calcification of bovine jugular veins and the underlying mechanism.

OBJECTIVES: To evaluate the effects of combined treatment with tannic acid and ferric ions on the biomechanical and anti-calcification properties of glutaraldehyde-fixed bovine jugular veins after xenografting. METHODS: Two-point bending test and uniaxial tensile test were used to evaluate the flexural and biomechanical properties; Subcutaneous implantation in rat and right ventricular outflow tract reconstruction of sheep were used to evaluate the anti-calcification effects; The performance of the graft in sheep models was evaluated every month after the surgery with echocardiography examination. Markers of macrophages, T lymphocytes, smooth muscle cell osteogenic differentiation and matrix metalloproteinases in sheep explants were detected by immunohistochemistry. RESULTS: The flexibility of the bovine jugular veins cotreated with ferric ions-tannic acid was improved while maintaining biomechanical properties and excellent anti-calcification effects. Echocardiography results showed that the grafts functioned well in the animals without stenosis or reflux of the valve. Immunohistochemical studies showed that the osteogenic differentiation marker (Runx2) was detected in calcified regions and colocalised with the SMC marker (α-SMA). Compared to the glutaraldehyde-treated samples, T-cell marker (CD3), matrix metalloproteinase-2 and 9 expressions were reduced in the ferric ions-tannic acid treated group. CONCLUSION: Ferric ions-tannic acid treatment can give the conduits better flexibility with excellent biomechanical properties and anti-calcification effects, making it a promising bovine jugular veins processing method.

Effect of valve leaflet surface patterning on valve hydrodynamic performance.

OBJECTIVE: We aimed to elucidate the effects of the micro-structure of the pyrolytic carbon for artificial heart valves on its hydrodynamic performance. METHODS: Bileaflet mechanical valves of GKS 23 and 29 A were randomly selected. According to ISO5840, mean transvalvular pressure (MPG), regurgitation fraction (RF), and effective orifice area (EOA) of valve were assessed. Then, parallel-groove pattern was constructed by laser etching on leaflet surface, and the valves were subjected again to the same test. RESULTS: Compared with before patterning at 2, 3.5, 5, and 7 L/min, the MPG of the valves in two specifications were higher, the EOA was larger in 23 A, but smaller in 29 A, and the RF was contrary to EOA. At 5 L/min, the RF in both specifications was lower after etching at 45 bpm. At 70 bpm however, the RF in 23 A decreased, in 29 A increased. CONCLUSION: The parallel-groove pattern on leaflet surface affected the hemodynamic performance of the valve prostheses.

Comparison of the Oral Microbiota Structure among People from the Same Ethnic Group Living in Different Environments.

The characteristics of the oral microbiota may depend on oral health, age, diet, and geography, but the influence of the geographic setting on the oral microbiota has received limited attention. The characteristics of oral microbiota have been reported to differ between urban and rural environments. In order to minimize the influence of genetic background, we recruited 54 volunteers from the same ethnic group, living in urban and rural areas of Gansu Province, China. We collected dental plaque samples and divided them into four groups according to the participant's area of residence and dental caries status. We sequenced the 16S rRNA of these samples using the Pacific Biosciences sequencing platform and analyzed the correlation between the geographic area and the characteristics of the oral microbiota. Analysis of the alpha and beta diversity revealed that there were significant differences in diversity and composition of dental plaque microflora among the four groups. Cluster analysis revealed that geographic area played an important role in determining the oral microbiota. Network analysis of oral microorganisms showed that geographic differences had major influence on the composition characteristics and internal structure of oral microorganisms. We found that some dominant strains which may play a key role in maintaining oral health, such as Streptococcus oralis, Capnocytophaga sputigena, Porphyromonas catoniae, Corynebacterium matruchotii, Haemophilus parainfluenzae, and Prevotella loescheii, were less affected by the geographic setting. These results provide a deeper understanding of factors influencing the composition of the oral microbiota and could contribute to early diagnosis and effective prevention of dental caries in different settings.

Interventional Microbubble Enhanced Sonothrombolysis on Left Ventricular Assist Devices.

The left ventricular assist device (LVAD) is often used in the treatment of heart failure. However, 4% to 9% implanted LVAD will have thrombosis problem in one year, which is fatal to the patient's life. In this work, an interventional sonothrombolysis (IST) method is developed to realize the thrombolysis on LVAD. A pair of ultrasound transducer rings is installed on the shell of LVAD, and drug-loaded microbubbles are injected into the LVAD through the interventional method. The microbubbles are adhere on the thrombus with the coated thrombus-targeted drugs, and the thrombolytic drugs carried by the bubbles are brought into the thrombus by the cavitation of bubbles under the ultrasound. In a proof-of-concept experiment in a live sheep model, the thrombus on LVAD is dissolved in 30 min, without damages on LVADs and organs. This IST exhibits to be more efficient and safer compared with other thrombolysis methods on LVAD.

An association analysis for genetic factors for dental caries susceptibility in a cohort of Chinese children.

OBJECTIVE: To comprehensively investigate the effects of 25 variants in 15 genes on dental caries susceptibility in a cohort of Chinese children. METHODS: A total of 25 variants in 15 genes were genotyped with MassARRAY iPLEX system and analyzed in 265 healthy controls and 254 children affected by dental caries with different dmft scores. The children with dental caries were stratified into "mild group" (scores from 1 to 3), "moderate group" (scores from 4 to 6), and "severe group" (scores from 7 to 14). RESULTS: The association analysis revealed that rs11362 of defensin ß1 (DEFB1) was significantly associated with dental caries susceptibility (OR = 2.447, p = 1.165E-04). Furthermore, rs11362 was positively correlated with the severity of dental caries. For another selected variant of DEFB1, rs1799946 was significantly associated with dental caries susceptibility in the severe group (OR = 0.473, p = 3.70E-03) and also significant in the group consisted of moderate and severe subjects (OR = 0.623, p = .033). The results from logistic regression in additive, dominant, and recessive models also exhibited the similar patterns. CONCLUSION: Out of 25 selected variants, only 2 of DEFB1 gene (rs11362 and rs1799946) were significantly associated with dental caries susceptibility in children.

Comparison of the community-acquired pneumonia and COVID-19 at the early stage: findings from two cohort studies.

BACKGROUND: The current focus is largely on whole course medical management of coronavirus disease-19 (COVID-19) with real-time polymerase chain reaction (RT-PCR) and radiological features, while the mild cases are usually missed. Thus, combination of multiple diagnostic methods is urgent to understand COVID-19 fully and to monitor the progression of COVID-19. METHODS: laboratory variables of 40 mild COVID-19 patients, 30 patients with community-acquired pneumonia (CAP) and 32 healthy individuals were analyzed by principal component analysis (PCA), Kruskal test, Procrustes test, the vegan package in R, CCA package and receiver operating characteristic to investigate the characteristics of the laboratory variables and their relationships in COVID-19. RESULTS: The correlations between the laboratory variables presented a variety of intricate linkages in the COVID-19 group compared with the healthy group and CAP patient group. The prediction probability of the combination of lymphocyte count (LY), eosinophil (EO) and platelets (PLT) was 0.847, 0.854 for the combination of lactate (LDH), creatine kinase isoenzyme (CK-MB), and C-reactive protein (CRP), 0.740 for the combination of EO, white blood cell count (WBC) and neutrophil count (NEUT) and 0.872 for the combination of CK-MB and P. CONCLUSIONS: The correlations between the laboratory variables in the COVID-19 group could be a unique characteristic showing promise as a method for COVID-19 prediction and monitoring progression of COVID-19 infection.

Fabrication of a gradient hydrophobic surface with parallel ridges on pyrolytic carbon for artificial heart valves.

Effective surface modification to endow pyrolytic carbon (PYC) with long-term anti-thrombotic performance is highly demanded. In this work, a gradient hydrophobic surface on PYC was prepared by creating parallel ridges via the combination of laser etching technology and surface fluorosilanization. Scanning electron microscopy (SEM) observation confirms that the gradient hydrophobic surface is composed of a bare PYC region and four regions of parallel ridges with varying distances. The gradient hydrophobic surface is stable in air, phosphate buffer solution (PBS), and flowing PBS. Additionally, the gradient hydrophobic surface on PYC shows spontaneous droplet motion and much lower flow resistance than bare PYC. Compared to bare PYC, the gradient hydrophobic surface on PYC exhibits better blood compatibility and anti-adhesion performance. The results presented in this paper confirm that creating a gradient hydrophobic surface is an effective way of achieving long-lasting anti-thrombosis property.

MicroRNA polymorphism: A target for diagnosis and prognosis of hepatocellular carcinoma?

Hepatocellular carcinoma (HCC) is a life-threatening cancer of the digestive system, with complex pathogenesis affected by a broad spectrum of genetic and epigenetic factors. Among several factors, microRNAs (miRNAs), which are considered regulators of the post-transcriptional gene expression, play important roles in determining the malignant phenotype of HCC. In recent years, the advances in molecular genetics have resulted in the characterization of complex genetic factors and in the identification of epigenetic mechanisms of diseases. Accumulating data have suggested that miRNA polymorphisms are involved in tumorigenesis and prognosis, suggesting that the miRNAs may serve as a target for HCC with regard to pathogenesis and prognosis. In the present review, a comprehensive and detailed literature search was conducted and the role of miRNA polymorphisms in the pathogenesis and prognosis of HCC is summarized. The data proposed the use of miRNAs as targets for the diagnosis and treatment of HCC.

Propagation source identification of infectious diseases with graph convolutional networks.

Source identification in networks has drawn considerable interest to understand and control the infectious disease propagation processes. It is usually difficult to achieve both high accuracy and short error distance when we try to solve the problem. This study attempts to introduce the graph convolutional network for the problem of source identification in a given network with different infection rates. First, we put forward a label propagation framework, which can locate the infection source based on both infected and uninfected nodes. Then, a novel Source Identification Graph Convolutional Network (SIGN) framework is proposed inspired by label propagation. Third, we modify the classical cross-entropy loss function and presented neighborhood loss to optimize the average error distance. Finally, extensive experiments are performed on eight datasets with different topologies and varying infection sizes to demonstrate the effectiveness of the proposed algorithms. We compare the proposed method with four mainstream approaches, and our method shows strong performances especially under the large infection size.

Source identification of infectious diseases in networks via label ranking.

BACKGROUND: Outbreaks of infectious diseases would cause great losses to the human society. Source identification in networks has drawn considerable interest in order to understand and control the infectious disease propagation processes. Unsatisfactory accuracy and high time complexity are major obstacles to practical applications under various real-world situations for existing source identification algorithms. METHODS: This study attempts to measure the possibility for nodes to become the infection source through label ranking. A unified Label Ranking framework for source identification with complete observation and snapshot is proposed. Firstly, a basic label ranking algorithm with complete observation of the network considering both infected and uninfected nodes is designed. Our inferred infection source node with the highest label ranking tends to have more infected nodes surrounding it, which makes it likely to be in the center of infection subgraph and far from the uninfected frontier. A two-stage algorithm for source identification via semi-supervised learning and label ranking is further proposed to address the source identification issue with snapshot. RESULTS: Extensive experiments are conducted on both synthetic and real-world network datasets. It turns out that the proposed label ranking algorithms are capable of identifying the propagation source under different situations fairly accurately with acceptable computational complexity without knowing the underlying model of infection propagation. CONCLUSIONS: The effectiveness and efficiency of the label ranking algorithms proposed in this study make them be of practical value for infection source identification.

Do Maternal Microbes Shape Newborn Oral Microbes?

Strong evidence suggests that the early composition of the oral microbiota of neonates plays an important role for the postnatal development of the oral health or immune system. However, the relationship between the maternal microbiome and the initial neonatal microbiome remains unclear. In this study, 25 pregnant women and their neonates were recruited, and the samples were collected from the maternal oral cavity, amniotic fluid, placenta and neonatal oral cavity. High-throughput sequencing of 16S rRNA was performed using the Illumina MiSeq platform to analyze the correlation with microbial community structure between the maternal and the neonatal oral cavity. The results indicated that the number of shared OTUs was up to 635 in four groups. The PCoA showed that there were certain similarities in the microbial community structure of the four groups. The dominant bacterial genera of the shared OTUs were consistent with human oral microbes, including Streptococcus, Fusobacterium and Prevotella. The results showed that there might be a correlation between the maternal and neonatal oral microbiome, through the amniotic fluid and placenta.

Modification of Mcl-1 alternative splicing induces apoptosis and suppresses tumor proliferation in gastric cancer.

Splicing dysregulation, which leads to apoptosis resistance, has been recognized as a major hallmark for tumorigenesis and cancer progression. Targeting alternative splicing by either increasing pro-apoptotic proteins or inhibiting anti-apoptotic proteins in tumor cells may be an effective approach for gastric cancer (GC) therapy. However, the role of modulation of alternative splicing in GC remains poorly understood. In this study, to the best of our knowledge, the unbalanced expression of the myeloid cell leukemia-1 (Mcl-1) splicing variants, Mcl-1L and Mcl-1S, was identified in GC patients for the first time. Increasing anti-apoptotic Mcl-1L and decreasing pro-apoptotic Mcl-1S expression levels were correlated with tumor proliferation and poor survival. In vitro data showed that a shift in splicing from Mcl-1L to Mcl-1S induced by treatment with Mcl-1-specific steric-blocking oligonucleotides (SBOs) efficiently decreased Mcl-1L expression, increased Mcl-1S expression, and accelerated tumor cell apoptosis in a dose-dependent manner. Additionally, mouse xenotransplant models confirmed that modification of Mcl-1 alternative splicing increased tumor cell death and suppressed tumor proliferation. This study demonstrated that the modification of Mcl-1 splicing might stimulate the pro-apoptotic factor and inhibit the anti-apoptotic protein to induce significant apoptosis. Thus, this finding provided a strategy for cancer therapy, according to which SBOs could be used to change the Mcl-1 splicing pattern, thereby inducing apoptosis.

Long-term results of triple-layered small diameter vascular grafts in sheep carotid arteries.

There is an urgent clinical for small diameter vascular grafts (SDVGs) for use in the treatment of coronary artery disease. Moreover, biodegradable SDVGs are drawing increasing attention because they have the potential to restore vascular function with the degradation of vascular graft and tissue regeneration. In this study, we designed triple-layered SDVGs to mimic the native arterial structure, with each layer contributing its unique porosity to the porous structure. We evaluated triple-layered SDVGs in a sheep carotid arterial replacement model. After implantation for 12 months, two grafts were patent and indicated the feasibility of using grafts in large animals. Nevertheless, it was determined that both grafts formed aneurysms at the proximal end. The prevention of such aneurysms remains a challenge for future investigation.

Controllable synthesis of biomimetic nano/submicro-fibrous tubes for potential small-diameter vascular grafts.

Mimicking the morphological structure of native blood vessels is critical for the development of vascular grafts. Herein, small-diameter composite vascular grafts that integrate the nanofibrous bacterial cellulose (BC) and submicrofibrous cellulose acetate (CA) were fabricated via a combined electrospinning and step-by-step in situ biosynthesis. Scanning electron microscopy (SEM) observation shows the nano/submicro-fibrous morphology and well-interconnected porous structure of the BC/CA grafts. It is found that the BC/CA graft with a suitable BC content demonstrates lower potential of thrombus formation and enhanced endothelialization as compared to the BC and CA counterparts. Western blotting and RT-qPCR results suggest that the BC/CA-2 graft promotes endothelialization by improving expressions of genes vWF-1 and CD31 and protein CD31. The in vivo tests demonstrate much lower inflammatory response to the BC/CA graft. These results suggest that the BC/CA graft shows a great potential as an artificial graft for rapid formation of an endothelial cell monolayer.

The correlations between Th1 and Th2 cytokines in human alveolar echinococcosis.

BACKGROUND: Alveolar echinococcosis (AE) is a zoonotic parasitic disease caused by Echinococcus multilocularis larval tapeworm infections in humans that severely impairs the health of affected patients in the northern hemisphere. METHODS: The expression levels of 20 cytokines associated with AE infection were measured by enzyme-linked immunosorbent assay, and the correlations between these cytokines were analysed in the R programming language. RESULTS: Serum cytokine levels differed among individuals in both the AE patient and healthy control groups. The results of the correlations among the cytokines showed obvious differences between the two groups. In the AE patients group, Th1 and Th2 cytokines formed a more complicated network than that in the healthy control group. CONCLUSIONS: The altered correlations between Th1 and Th2 cytokines may be closely associated with AE infection, which may provide a new explanation for the essential differences between AE patients and healthy individuals.

Laser-induced wettability gradient surface on NiTi alloy for improved hemocompatibility and flow resistance.

Blood contacting materials with anti-thrombotic surfaces are highly demanded in clinics. Despite considerable research on surface modifications, limited progress has been made on effective prevention of thrombosis for artificial implants such as mechanical valve prosthesis. Herein, wettability gradient surface, which can ideally exhibit good hemocompatibility and low flow resistance, was developed for potential reduction of thrombosis. The wettability gradient surface on a model substrate of nickel-titanium (NiTi) alloy was prepared via a simple and economic method that combined laser microfabrication and surface stearic acid self-assembly approach. Scanning electron microscopy (SEM) observation confirmed that the wettability gradient surface was composed of a smooth NiTi region and three porous regions with different pore sizes and distances. Contact angle measurement revealed that, together with a low surface energy layer, the structural topography gradient could create a wettability gradient surface on NiTi alloy which could drive droplet motion. When compared with bare NiTi, such wettability gradient surface exhibited better anti-adhesion property, which was beneficial to the hemocompatibility and thus showing a lower hemolysis rate. Additionally, the wettability gradient surface also showed much lower flow resistance than bare NiTi. These results demonstrate that the developed wettability gradient surface may be used to reduce thrombosis.

[Design of an axial blood pump of diffuser with splitter blades and cantilevered main blades].

An implantable axial blood pump was designed according to the circulation assist requirement of severe heart failure patients of China. The design point was chosen at 3 L/min flow rate with 100 mm Hg pressure rise when the blood pump can provide flow rates of 2-7 L/min. The blood pump with good hemolytic and anti-thrombogenic property at widely operating range was designed by developing a structure that including the spindly rotor impeller structure and the diffuser with splitter blades and cantilevered main blades. Numerical simulation and particle image velocimetry (PIV) experiment were conducted to analyze the hydraulic, flow fields and hemolytic performance of the blood pump. The results showed that the blood pump could provide flow rates of 2-7 L/min with pressure rise of 60.0-151.3 mm Hg when the blood pump rotating from 7 000 to 11 000 r/min. After adding the splitter blades, the separation flow at the suction surface of the diffuser has been reduced efficiently. The cantilever structure changed the blade gap from shroud to hub that reduced the tangential velocity from 6.2 m/s to 4.3-1.1 m/s in blade gap. Moreover, the maximum scalar shear stress of the blood pump was 897.3 Pa, and the averaged scalar shear stress was 37.7 Pa. The hemolysis index of the blood pump was 0.168% calculated with Heuser's hemolysis model. The PIV and simulated results showed the overall agreement of flow field distribution in diffuser region. The blood damage caused by higher shear stress would be reduced by adopting the spindle rotor impeller and diffuser with splitter blades and cantilevered main blades. The blood could flow smoothly through the axial blood pump with satisfactory hydraulics performance and without separation flow.

Association of ENAM, TUFT1, MMP13, IL1B, IL10 and IL1RN gene polymorphism and dental caries susceptibility in Chinese children.

OBJECTIVE: To investigate the association between single nucleotide polymorphisms (SNPs) in six candidate genes (enamelin [ ENAM]; tuftelin 1 [ TUFT1]; matrix metallopeptidase 13 [ MMP13]; interleukin 1 beta [ IL1B]; interleukin 10 [ IL10]; interleukin 1 receptor antagonist [ IL1RN]) and dental caries in children from northwest China. METHODS: This case-control study enrolled children (12-15 years) who underwent routine dental examinations. The children were divided into two groups based on the presence of dental caries. A saliva sample was collected and seven SNPs (rs3806804A/G in ENAM, rs3811411T/G in TUFT1, rs2252070A/G and rs597315A/T in MMP13, rs1143627C/T in IL1B, rs1800872A/C in IL10 and rs956730G/A in IL1RN) were genotyped. RESULTS: A total of 357 children were enrolled in the study: 161 with dental caries and 196 without dental caries. No significant difference was found in the alleles and genotypes of five genes ( ENAM, TUFT1, MMP13, IL10 and IL1RN) between those with and without dental caries. A significant relationship was found between the IL1B rs1143627C/T polymorphism and dental caries susceptibility with those carrying the rs1143627CT genotype having a lower risk of dental caries compared with those carrying the CC genotype (odds ratio 0.557; 95% confidence interval 0.326, 0.952). CONCLUSION: The IL1B rs1143627C/T polymorphism may be associated with dental caries susceptibility in children from northwest China.

Numerical investigation of the influence of a bearing/shaft structure in an axial blood pump on the potential for device thrombosis.

Adverse events caused by flow-induced thrombus formation around the bearing/shaft of an axial blood pump remain a serious problem for axial blood pumps. Moreover, excessive anticoagulation with thrombosis around the bearing potentially increases the risk of postoperative gastrointestinal bleeding. The purpose of this study is to analyze the influence of the bearing structure on the thrombosis potential of an axial blood pump. The bearing/shaft structure was embedded into an axial blood pump numerical model. The numerical simulation and analysis are focused on the low wall shear stresses, recirculation, and residence time close to the bearing region to evaluate the potential for thrombosis around the bearing. Then, the flow field near the blood pump bearing was tested via in vitro particle image velocimetry experiments to verify the numerical results. The simulation results showed that after embedding the bearing/shaft structure a recirculation zone appeared in the outlet guide vane bearing/shaft region, the residence time increased 11-fold in comparison to the pump without the bearing/shaft structure, the scalar shear stress in the shaft surface was less than 7.8 Pa, and the stress accumulation was less than 0.10 Pa s. The numerical results showed that platelets that flow through the bearing region are exposed to significantly lower wall shear stress and a longer residence time, leading to activated platelet adhesion. The reduced stress accumulation and increased time in the bearing region lead to increased platelet activation.