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Gastric precancerous lesion (GPL) is a crucial stage in the development of gastric cancer, characterized by incomplete intestinal epithelial chemotaxis and heterogeneous hyperplasia with high malignant potential. Early intervention in GPL is vital for preventing gastric cancer. Additionally, there are shared risk factors and pathogenesis between tumors and coronary heart disease (CHD), with an increasing number of tumor patients GPL complicated with CHD due to improved survival rates. Reperfusion therapy in CHD can result in myocardial ischemia-reperfusion injury (MIRI). Traditional Chinese medicine (TCM) has demonstrated unique advantages in treating GPL and MIRI by promoting blood circulation and removing blood stasis. Panax ginseng total saponin (PNS), a component of TCM known for its blood circulation benefits, has shown positive effects in inhibiting tumor growth and improving myocardial ischemia. This study utilized a GPL-MIRI mouse model to investigate the effects of PNS in treatment. Results indicated that PNS significantly improved typical GPL lesions in mice, such as incomplete intestinal epithelialization and heteroplasia, and also reduced myocardial infarction. At the molecular level, PNS exhibited a bidirectional regulatory role in the GPL-MIRI model. It enhanced the autophagic process in gastric mucosal cells by inhibiting the PI3K/Akt/mTOR signaling pathway, while suppressed excessive autophagy in cardiomyocytes. These findings offer new insights and treatment strategies for managing GPL and MIRI using the TCM compound PNS.

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Background: Statins, being the primary pharmacological intervention for hypercholesterolemia, exhibit a notable degree of interpatient variability in their effectiveness, which may be associated with gut microbiota. This study sought to identify the biomarkers for evaluating differences in statin efficacy. Methods: A quasi case-control study was conducted among participants with hypercholesterolemia and coronary heart disease taking rosuvastatin essential. According to the level of low density lipoprotein cholesterol (LDL-C), participants was divided into the "Up to standard" (US) group and the "Below standard" (BS) group. 16S rDNA sequencing and untargeted metabolomics were applied to detected the information of gut microbiota and related metabolites. Results: A total of 8 US and 8 BS group matched by age and sex were included in the final analysis. 16S rDNA sequencing results indicated that the characteristic strains of the US group were f-Eubacterium_coprostanoligenes and g-Papillibacter, while the characteristic flora of the BS group were o-C0119, g-Pseudolabrys, s-Dyella-Marensis and f-Xanthobacaceae. Metabolomic results suggested that the levels of chenodeoxycholic acid-3-ß-D-glucuronide, 1-methylnicotinamide and acetoacetate in stool samples of the US group were significantly higher than those of the BS group. By identifying the differentially abundant bacterial taxa, the gut microbiota could modulate the efficacy of statins through producing enzymes involved in cholesterol metabolism. Conclusions: The findings suggest that the difference in statin efficacy may be related to gut microbiota strains that can produce short-chain fatty acids and secondary bile acids and affect the efficacy of statins by regulating the activities of cholesterol metabolite-related proteins. Metabolites related to short-chain fatty acids and secondary bile acids in the gut are expected to be biomarkers indicating the efficacy of statins.

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Mechanical properties, as crucial physical properties, have a significant impact on the occurrence, development, and metastasis of tumors. Regulating the mechanical properties of tumors to enhance their sensitivity to radiotherapy and chemotherapy has become an important strategy in the field of cancer treatment. Over the past few decades, nanomaterials have made remarkable progress in cancer therapy, either based on their intrinsic properties or as drug delivery carriers. However, the investigation of nanomaterials of mechanical regulation in tumor therapy is currently in its initial stages. The mechanical properties of nanomaterials themselves, drug carrier targeting, and regulation of the mechanical environment of tumor tissue have far-reaching effects on the efficient uptake of drugs and clinical tumor treatment. Therefore, this review aims to comprehensively summarize the applications and research progress of nanomaterials in tumor therapy based on the regulation of mechanical properties, in order to provide strong support for further research and the development of treatment strategies in this field.

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PURPOSE: To establish a psychometric validated pelvic fracture-urethral injury postoperative erectile function patient reported outcome measure (PFUI pEF PROM). We also aim to explore PFUI patients' potential classification and suitable postoperative erectile function assessment pattern. METHODS: A total of 93 PFUI patients who treated by excision and primary anastomotic (EPA) urethroplasty from January 2020 to August 2022 were enrolled to this study. Patients who had intercourse completed the IIEF-5, those who had sexual stimulation other than intercourse finished PFUI pEF PROM, and those who performed both completed the IIEF-5, and PFUI pEF PROM. Erection Hardness Score (EHS) was completed by all patients. This PROM was performed psychometric validation and used to find PFUI patients potential classification through latent class analysis. Then, we determined the cut-off value though receiver-operating characteristic (ROC) curve and performed univariate analysis subgroups feature. RESULTS: The PFUI pEF PROM demonstrated high reliability and validity with a Cronbach's alpha of 0.928. It correlated significantly with IIEF-5 (r = 0.550, p < 0.001) and EHS (r = 0.909, p < 0.001). The latent class analysis identified three patient subgroups, with 14.5 as the subgroup cut-off value. Urethral stricture length, IIEF-5, and EHS score were identified as influence factors for maximal erection potential. An assessment pattern combining IIEF-5, EHS, and the PFUI pEF PROM covered 92.5% of patients. CONCLUSION: This PROM effectively addresses the current limitation in assessing erectile function in PFUI patients. This study provides a promising tool for stratified assessment, prediction erection recovery, and treatment guidance in the PFUI Erectile dysfunction field.

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Context: Oral mucosa graft (OMG) and penile skin flap (PSF) are common substitutions in urethroplasty; however, the recommended substitution for anterior urethral strictures remains uncertain. Objective: To compare the efficacy of OMG and PSF in anterior urethral strictures in terms of success rate and prevalence of postvoid dribbling based on current studies. Evidence acquisition: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and registered at PROSPERO (ID: CRD42022313879). All publications until March 1, 2022, were searched in the PubMed, EMBASE, and Cochrane Library databases without any restriction. Studies that focused on patients with anterior urethral strictures undergoing single-stage augmentation urethroplasty with OMG and PSF, and reported comparable success rates between the two substitutions were included. Evidence synthesis: Thirteen studies involving a total of 1216 patients were included in the screening procedures, and 12 studies were eventually included in the meta-analysis. No significant difference in success rates was identified between OMG and PSF (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 0.96-2.07, p = 0.08). No significant difference was observed in the comparison of success rates in penile urethral strictures (OR: 0.95, 95% CI: 0.53-1.70, p = 0.86) and in the comparison of postvoid dribbling (OR: 0.59, 95% CI: 0.31-1.11, p = 0.10). However, a subgroup analysis suggested that OMG had a higher success rate than PSF in studies with the top 50% sample size (six studies, OR: 1.678, 95% CI: 1.055-2.668, p = 0.029) and the top 50% follow-up period (five studies, OR: 2.279, 95% CI: 1.193-4.352, p = 0.013). Conclusions: OMG provides the same success rate and postvoid dribbling as PSF. However, based on the existing evidence, OMG is more likely to perform better in a cohort with long-term follow-up and a relatively large sample size. More studies on the two substitutions are necessary to evaluate the factors of urethroplasty success rate, performance of substitutions in penile urethral strictures, and indicators of quality of life. Patient summary: In this research, we compared the outcomes of oral mucosa graft (OMG) and penile skin flap for urethroplasty in anterior urethral stricture patients in 13 studies. We found that these were similar in terms of success rate and postvoid dribbling. However, OMG could probably provide a higher success rate when the studies had more patients or a longer follow-up period.

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Romanesque and Gothic are two types of deformed aortic arch geometries after surgical repair of coarctation of the aorta. The abnormal arch geometry and hemodynamics are associated with late systemic hypertension, aortic aneurysms, and other cardiovascular complications. To understand the fluid dynamic signatures of such flow, a combined experimental and computational fluid dynamic (CFD) study has been conducted to quantitatively compare the main (axial) and secondary flow characteristics. In the experiments, a pulsatile flow simulator was used to generate the pulsatile flow conditions. Phase-locked planar and tomographic particle image velocimetry techniques were employed to quantitatively study the flow fields. Three-dimensional CFD simulations were also performed and compared with the experimental data. The results show that in the Romanesque arch, the flow first accelerates along the inner wall and then becomes more uniform in the cross-section after the peak systole. A pair of wall vortices and Dean-type vortices develop during the systolic phase. The coherent structures are continuously extended into the descending aorta and persist throughout the cycle. In comparison, the Gothic arch exhibits a highly skewed velocity distribution with high velocity around the arch apex. The sharp curvature causes flow separation, jet impingement, and stagnant flow near the top. The coherent structures in the Gothic arch are less continuous in the descending aorta, which also differ from those observed in the Romanesque model. The distinct flow characteristics of the Gothic arch lead to more temporal and spatial variations of wall shear stress in the descending aorta, implying hemodynamic risks for aortic complications.

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The mortality rate of liver cancer is gradually increasing worldwide due to the increasing risk factors such as fatty liver, diabetes, and alcoholic cirrhosis. The diagnostic methods of liver cancer include ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI), among others. The treatment of liver cancer includes surgical resection, transplantation, ablation, and chemoembolization; however, treatment still faces multiple challenges due to its insidious development, high rate of recurrence after surgical resection, and high failure rate of transplantation. The emergence of liposomes has provided new insights into the treatment of liver cancer. Due to their excellent carrier properties and maneuverability, liposomes can be used to perform a variety of functions such as aiding in imaging diagnoses, combinatorial therapies, and integrating disease diagnosis and treatment. In this paper, we further discuss such advantages.

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Built on the hybrid immersed boundary/finite element (IB/FE) method, fluid-structure interaction (FSI) simulations of aortic valve (AV) dynamics are performed with three different constitutive laws and two different fiber architectures for the AV leaflets. An idealized AV model is used and mounted in a straight tube, and a three-element Windkessel model is further attached to the aorta. After obtaining ex vivo biaxial tensile testing of porcine AV leaflets, we first determine the constitutive parameters of the selected three constitutive laws by matching the analytical stretch-stress relations derived from constitutive laws to the experimentally measured data. Both the average error and relevant R-squared value reveal that the anisotropic non-linear constitutive law with exponential terms for both the fiber and cross-fiber directions could be more suitable for characterizing the mechanical behaviors of the AV leaflets. We then thoroughly compare the simulation results from both structural mechanics and hemodynamics. Compared to the other two constitutive laws, the anisotropic non-linear constitutive law with exponential terms for both the fiber and cross-fiber directions shows the larger leaflet displacements at the opened state, the largest forward jet flow, the smaller regurgitant flow. We further analyze hemodynamic parameters of the six different cases, including the regurgitant fraction, the mean transvalvular pressure gradient, the effective orifice area, and the energy loss of the left ventricle. We find that the fiber architecture with body-fitted orientation shows better dynamic behaviors in the leaflets, especially with the constitutive law using exponential terms for both the fiber and cross-fiber directions. In conclusion, both constitutive laws and fiber architectures can affect AV dynamics. Our results further suggest that the strain energy function with exponential terms for both the fiber and cross-fiber directions could be more suitable for describing the AV leaflet mechanical behaviors. Future experimental studies are needed to identify competent constitutive laws for the AV leaflets and their associated fiber orientations with controlled experiments. Although limitations exist in the present AV model, our results provide important information for selecting appropriate constitutive laws and fiber architectures when modeling AV dynamics.

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Bioprosthetic valves are widely used for aortic valve replacements for patients with severe aortic diseases. However, tissue-engineered leaflets normally deteriorate over time due to calcification, leading to life-threatening conditions that would require re-operation. The hemodynamics induced by a prosthetic stenosis is complicated and not fully understood. This in vitro experimental study focuses on the fluid dynamics of two aortic valve models with different prosthetic stenosis conditions. An in vitro cardiovascular flow simulator was utilized to provide the pulsatile physiological flow conditions. Phase-locked particle image velocimetry (PIV) and high-frequency pressure sensors were employed to measure the flow fields and pressure waveforms. Pressure data were evaluated for the two models representing moderate and severe stenosis conditions, respectively. The severe prosthetic stenosis induced a prolonged ejection period and increased acceleration time ratio. PIV results suggest the severe prosthetic stenosis resulted in a two-fold increase in peak jet velocity and a three-fold increase in peak turbulence kinetic energy compared to the moderate stenosis case. The severe stenosis also caused rapid expansion of the jet downstream of the valve orifice and increased eccentricity of the jet flow. The maximum Reynolds shear stress in the severe stenosis case was found similar to the bileaflet mechanical valve reported by previous literature, which was below the risk threshold of blood cell damage but could potentially increase the risks of platelet activation and aggregation.

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Liquid storage of spermatozoa is important for artificial insemination and herd genetic breeding. However, the extended time of storage inducing the rapid decline in spermatozoa quality limits the development of this technology. The molecular mechanisms underlying liquid storage of spermatozoa remain largely unexplored. In this study, the effects of liquid storage on functional quality of spermatozoa were assessed in goat (Capra hircus). The time-dependent decline in spermatozoa motility showed a strong correlation with the significant increase in apoptosis. Moreover, apoptosis-related ultrastructural changes were observed, especially the defects in mitochondria. A significant decrease in mitochondrial membrane potential and changes in the expression of mitochondrial apoptosis-related proteins indicated mitochondrial dysfunction and mitochondrial apoptotic pathway activation. Notably, the abnormally high level of reactive oxygen species (ROS) caused by liquid storage resulted in oxidative damage to mitochondria and accelerated mitochondria-dependent apoptosis, as demonstrated by the addition of ROS scavenger N-acetylcysteine. Furthermore, critical differentially expressed proteins involved in mitochondria-dependent apoptosis and antioxidant defense were identified and profiled by quantitative proteomic analysis, facilitating the understanding of molecular regulation of ROS-induced mitochondria-dependent apoptosis. These outcomes provide insights into the mechanisms underlying liquid storage of goat spermatozoa and enhance the progress of semen storage technology.

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In this paper, three different constitutive laws for mitral leaflets and two laws for chordae tendineae are selected to study their effects on mitral valve dynamics with fluid-structure interaction. We first fit these three mitral leaflet constitutive laws and two chordae tendineae laws with experimental data. The fluid-structure interaction is implemented in an immersed boundary framework with finite element extension for solid, that is the hybrid immersed boundary/finite element(IB/FE) method. We specifically compare the fluid-structure results of different constitutive laws since fluid-structure interaction is the physiological loading environment. This allows us to look at the peak jet velocity, the closure regurgitation volume, and the orifice area. Our numerical results show that different constitutive laws can affect mitral valve dynamics, such as the transvalvular flow rate, closure regurgitation and the orifice area, while the differences in fiber strain and stress are insignificant because all leaflet constitutive laws are fitted to the same set of experimental data. In addition, when an exponential constitutive law of chordae tendineae is used, a lower closure regurgitation flow is observed compared to that of a linear material model. In conclusion, combining numerical dynamic simulations and static experimental tests, we are able to identify suitable constitutive laws for dynamic behaviour of mitral leaflets and chordae under physiological conditions.

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